Nevin Manimala

Injury. 2021 Jun 2:S0020-1383(21)00492-7. doi: 10.1016/j.injury.2021.05.042. Online ahead of print.

ABSTRACT

AIMS: National guidelines set standards for the definitive management of open fractures within 72 h. This study aims to investigate our outcomes where this timeline was unachievable for most cases due to a split-site orthoplastic service.

PATIENTS & METHODS: 116 consecutive Gustilo-Anderson grade IIIB & IIIC open tibial fractures presenting to our major trauma centre (MTC) between September 2012 and April 2018 were reviewed. The mean follow up was 46 months (17 to 88). 110 (95%) were grade IIIB and 6 (5%) grade IIIC. The most common injury mechanism included road traffic accidents (59%) and falls (28%). Primary outcomes were recorded according to; timing of initial debridement and definitive cover, rates of superficial and deep infection, non-union and amputation. Subgroups were statistically analysed according to time to initial debridement, definitive soft-tissue cover and injury severity score (ISS).

RESULTS: The mean time to initial debridement was 11.3 h (2.9 to 38.9) and definitive soft-tissue cover 9.9 days (0 to 37). We recorded rates of: superficial infection; 42 cases (36%), deep infection; 14 cases (12%) and non-union requiring revision; 19 cases (16%). There were 20 amputations (17%) with 9 (8.6%) performed early and 11 (9.5%) delayed. Subgroup analysis showed higher rates of superficial infection (50%, p = 0.002) and amputation (26.6%, p = 0.01) for those debrided <12 h. A greater presenting ISS related to a delay to definitive cover >7 days (p = 0.05). Primary outcomes trended worse for those covered >7 days but did not reach significance.

CONCLUSION: Major trauma patients are particularly vulnerable to poor outcomes resulting from the delay in definitive management of open fractures. MTC’s need resources and a co-located orthoplastic service to achieve national standards and better outcomes. Current guidelines do not advise for the management of patients where a delay in definitive surgery is anticipated.

PMID:34158158 | DOI:10.1016/j.injury.2021.05.042

Palliat Support Care. 2021 Jun 23:1-6. doi: 10.1017/S1478951521000973. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of the study was to explore the proportion of adult patients and next-of-kin who had end-of-life (EOL) discussions and associated factors.

METHOD: A retrospective nationwide registry study was reported with data from the Swedish Register of Palliative Care. All patients in Sweden in hospitals, nursing homes, own homes, community, and palliative care units during 2015-2017 and their next-of-kin were included. Data were reported to the register by healthcare staff, based on diseased patients’ records regarding their last days of life, and were voluntary. Descriptive statistics illustrated the proportion of patients/next-of-kin who had EOL discussions and logistic regressions were used to examine associated factors.

RESULTS: About half of the patients (46%) did have an EOL discussion, but a third (32%) did not. Associated factors of those who did not have an EOL discussion were dementia (48.5%) or stroke (47.5%), older age (38.4%), being female (33.6%), being cared for in a nursing home (41.3%), or hospital (40.3%), having lost decision-making ability months before death (58.9%), and not having a documented decision to shift to EOL care (82.7%). Younger patients diagnosed with cancer and cared for at a palliative unit were more likely to have EOL discussions. The regression analysis showed similar results for next-of-kin.

SIGNIFICANCE OF RESULTS: The result shows that not all patients with palliative care needs have equal access to EOL discussions, despite efforts at a national level and the recognized benefits of timely communication about the EOL care. Further efforts must be made to achieve EOL discussions for all patients.

PMID:34158146 | DOI:10.1017/S1478951521000973

Psychol Med. 2021 Jun 23:1-9. doi: 10.1017/S0033291721001975. Online ahead of print.

ABSTRACT

This article casts a critical eye over the development of American psychiatry from 1980 to the present. It notes the rapid decline of psychoanalysis that followed the publication of DSM III; the rising influence of genetics and neuroscience; the re-emphasis on the biology of mental illness; and the collapse of public psychiatry that accompanied deinstitutionalization. It argues that while genetics and neuroscience have made scientific progress, the clinical utility of their findings to date has been very limited. The fifth edition of the DSM was supposed to base itself on this new science but that proved impossible. Diagnosis remains purely phenomenological and controversial. One of the ironies of research on psychiatric genetics is that has failed to find either a Mendelian origin of schizophrenia and depression or to validate the importance of hypothesized candidate genes. Genome-wide association studies have instead uncovered risk factors for major mental illnesses, but these overlap considerably, and the genetic associations are not dispositive. Most of those who carry these genetic variants do not develop mental illness. The status of psychopharmacology since the mid-1950s is scrutinized, as is the influence of the pharmaceutical industry on contemporary psychiatry, and the implications of its recent decision to abandon work in this arena. The paper concludes with an assessment of the crisis that it contends confronts contemporary American psychiatry: its overemphasis on biology; the urgent questions that persist about diagnosis and therapeutics; concerns about the directions of future research; and its inability to reduce the excess mortality that plagues the mentally ill.

PMID:34158141 | DOI:10.1017/S0033291721001975

J Pharm Policy Pract. 2021 Jun 22;14(1):53. doi: 10.1186/s40545-021-00330-x.

ABSTRACT

BACKGROUND: With the approval of biosimilars for subcutaneously administered products, such as adalimumab, etanercept and insulin, biosimilars become increasingly available in ambulatory care. Little is known about the knowledge and attitudes of healthcare providers who are in charge of dispensing and prescribing biosimilars in this context. This study aims to assess the knowledge and perception about biosimilars among community pharmacists and physicians.

METHODS: Belgian community pharmacists (n = 177) and physicians (n = 30) were surveyed on their knowledge, experience with dispensing/prescribing biologicals including biosimilars, perception regarding interchangeability, switching and substitution and informational and educational needs. Descriptive and statistical analyses were performed.

RESULTS: Only 32% of community pharmacists and 52% of physicians had yet dispensed/prescribed a biosimilar. Approximately 35% of community pharmacists felt insufficiently trained to counsel patients with biosimilar therapy, which was significantly higher compared to their self-assessed competence to counsel patients with biological therapy in general (p = 0.023). Community pharmacists experienced questions about similarity between reference products and biosimilars (47%) and their interchangeability (42%). Over 40% of physicians found patient uncertainty about efficacy and safety challenging when prescribing biosimilars. A similar proportion of physicians would only prescribe a biosimilar in indications for which the biosimilar has been tested clinically. The majority of pharmacists (58%) was in favor of substitution of biologicals, on the condition that the prescriber would be contacted. Also over 40% of physicians was open to this approach in case of substitution. Educational support, budget for additional staff and transparency about savings were considered suitable stimuli to incentivize biosimilar use. The need for information about biologicals including biosimilars was nearly unanimous among community pharmacists. Also 67% of physicians requested more information. Both community pharmacists and physicians preferred to be informed by their respective professional associations.

CONCLUSIONS: This study showed a substantial need for targeted educational measures to increase the knowledge and confidence about both biological medicines in general and biosimilars in particular among Belgian community pharmacists and physicians. The results may inform educational and policy measures to stimulate biosimilar use in ambulatory care.

PMID:34158128 | DOI:10.1186/s40545-021-00330-x

Stem Cell Res Ther. 2021 Jun 22;12(1):360. doi: 10.1186/s13287-021-02435-1.

ABSTRACT

BACKGROUND: Mesenchymal stem or stromal cells are the most widely used cell therapy to date. They are heterogeneous, with variations in growth potential, differentiation capacity and protein expression profile depending on tissue source and production process. Nomenclature and defining characteristics have been debated for almost 20 years, yet the generic term ‘MSC’ is used to cover a wide range of cellular phenotypes. Against a documented lack of definition of cellular populations used in clinical trials, our study evaluated the extent of characterisation of the cellular population or study drug.

METHODS: A literature search of clinical trials involving mesenchymal stem/stromal cells was refined to 84 papers upon application of pre-defined inclusion/exclusion criteria. Data were extracted covering background trial information including location, phase, indication, tissue source and details of clinical cell population characterisation (expression of surface markers, viability, differentiation assays and potency/functionality assays). Descriptive statistics were applied, and tests of association between groups were explored using Fisher’s exact test for count data with simulated p value.

RESULTS: Twenty-eight studies (33.3%) include no characterisation data. Forty-five (53.6%) reported average values per marker for all cell lots used in the trial, and 11 (13.1%) studies included individual values per cell lot. Viability was reported in 57% of studies. Differentiation was discussed: osteogenesis (29% of papers), adipogenesis (27%), and chondrogenesis (20%) and other functional assays arose in 7 papers (8%). The extent of characterisation was not related to the clinical phase of development. Assessment of functionality was very limited and did not always relate to the likely mechanism of action.

CONCLUSIONS: The extent of characterisation was poor and variable. Our findings concur with those in other fields including bone marrow aspirate and platelet-rich plasma therapy. We discuss the potential implications of these findings for the use of mesenchymal stem or stromal cells in regenerative medicine, and the importance of characterisation for transparency and comparability of literature.

PMID:34158116 | DOI:10.1186/s13287-021-02435-1

Infect Agent Cancer. 2021 Jun 22;16(1):45. doi: 10.1186/s13027-021-00388-x.

ABSTRACT

BACKGROUND: In December 2019 an outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 was first observed in Wuhan, China. The virus has spread rapidly throughout the world creating a pandemic scenario. Several risk factors have been identified, such as age, sex, concomitant diseases as well as viral load. A key point is the role of asymptomatic people in spreading SARS-CoV-2. An observational study in Southern Italy was conducted in order to elucidate the possible role of asymptomatic individuals related to their viral loads in the transmission of the virus within two nursing facilities.

METHODS: Oro-nasopharyngeal swabs from 179 nursing health care workers and patients were collected. SARS-CoV-2 RT-qPCR was performed and viral loads were calculated by using standard curve. A statistical correlation between viral loads, the presence/absence of symptoms, age and sex variables was investigated.

RESULTS: SARS-CoV-2 was confirmed in the 50.8 % (n = 91) of the cases. Median age of positive individuals resulted higher than negative ones. Over 65 year as well as female individuals showed higher susceptibility to SARS-CoV-2 infection, OR = 3.93 and 2.86, respectively. Among 91 tested positive, the 70.3 % was symptomatic while the 29.7 % was asymptomatic. Median viral loads of asymptomatic individuals were found statistically significant higher than symptomatic ones (p = 0.001), while no influence was observed in age and sex variables. The presence of comorbidities was 8.9 folds higher in patients who showed and developed symptoms compared to non-symptomatic ones. Moreover, higher viral loads were found in patients who remained asymptomatic than pre-symptomatic (p = 0.022).

CONCLUSIONS: A range from 9.2 to 69 % of confirmed SARS-CoV-2 cases remains asymptomatic, moreover, sporadic transmissions from asymptomatic people are reported, that makes their involvement an important issue to take into account in the spreading control of the virus. An asymptomatic clinical course was observed in the 29.7 % of positive individuals, moreover, median viral loads resulted to be statistically significant when compared to symptomatic ones. Surely, such a relevant frequency should not be ignored in relation to the spread of the disease in an environment which has not only important intrinsic (age, sex, concomitant diseases) but also extrinsic factors such as high population density and close contacts.

PMID:34158108 | DOI:10.1186/s13027-021-00388-x

J Cardiothorac Surg. 2021 Jun 22;16(1):179. doi: 10.1186/s13019-021-01558-z.

ABSTRACT

BACKGROUND: Obesity is dramatically increasing worldwide, and more obese patients may develop aortic dissection and present for surgical repair. The study aims to analyse the impact of body mass index (BMI) on surgical outcomes in patients with acute Stanford type A aortic dissection (ATAAD).

METHODS: From January 2017 to June 2019, the clinical data of 268 ATAAD patients in a single centre were retrospectively reviewed. They were divided into three groups based on the BMI: normal weight (BMI 18.5 to < 25 kg/m², n = 110), overweight (BMI 25 to < 30 kg/m², n = 114) and obese (BMI ≥30 kg/m², n = 44).

RESULTS: There was no statistical difference among the three groups in terms of the composite adverse events including 30-day mortality, stroke, paraplegia, renal failure, hepatic failure, reintubation or tracheotomy and low cardiac output syndrome (20.9% vs 21.9% vs 18.2% for normal, overweight and obese, respectively; P = 0.882). No significant difference was found in the mid-term survival among the three groups. The proportion of prolonged ventilation was highest in the obese group followed by the overweight and normal groups (59.1% vs 45.6% vs 34.5%, respectively; P = 0.017). Multivariable logistic regression analysis suggested that BMI was not associated with the composite adverse events, while BMI ≥30 kg/m² was an independent risk factor for prolonged ventilation (OR 2.261; 95% CI 1.056-4.838; P = 0.036).

CONCLUSIONS: BMI had no effect on the early major adverse outcomes and mid-term survival after surgery for ATAAD. Satisfactory surgical outcomes can be obtained in patients with ATAAD at all weights.

PMID:34158094 | DOI:10.1186/s13019-021-01558-z

Reprod Biol Endocrinol. 2021 Jun 22;19(1):94. doi: 10.1186/s12958-021-00777-2.

ABSTRACT

BACKGROUND: The male and female prostates are controlled by steroid hormones, suffering important morphological and physiological changes after castration. Prolactin is involved in the regulation of the male prostate, having already been identified in the tissue, acting through its receptor PRLR. In the Mongolian gerbil, in addition to the male prostate, the female prostate is also well developed and active in its secretion processes. The aim of the present study was to evaluate the effects of exposure to exogenous prolactin in the prostate of both intact and castrated male and female gerbils in order to establish if prolactin administration can sustain prostate cell activity in conditions of sexual hormone deprivation.

METHODS: The morphological analyses were performed by biometric analysis, lesion histological analysis and morphometric-stereological aspects. In addition, immune-cytochemical tests were performed for prolactin and its receptor, as well as for the receptors of androgen and oestrogen and serum prolactin dosage. All data were submitted to ANOVA or Kruskal-Wallis tests for comparison between groups. P < 0.05 was considered to be statistically significant.

RESULTS: The results showed a strong influence of prolactin on the morphology of the prostate, with the development of important epithelial alterations, after only 3 days of administration, and an expressive epithelial cell discard process after 30 days of administration. Prolactin acts in synergy with testosterone in males and mainly with oestrogens in females, establishing different steroid hormonal receptor immunoreactivity according to sex. It was also demonstrated that prolactin can assist in the recovery from some atrophic effects caused in the gland after castration, without causing additional tissue damage.

CONCLUSIONS: The prolactin and its receptor are involved in the maintenance of the homeostasis of male and female gerbils, and also cause distinct histological alterations after exogenous exposure for 3 and 30 days. The effects of prolactin are related to its joint action on androgens and oestrogens and it can also assist in the recovery from the atrophic effects of castration.

PMID:34158080 | DOI:10.1186/s12958-021-00777-2

Radiat Oncol. 2021 Jun 22;16(1):112. doi: 10.1186/s13014-021-01835-0.

ABSTRACT

BACKGROUND: The hippocampus is a critical organ for irradiation. Thus, we explored changes in hippocampal volume according to the dose delivered and the location relative to the glioblastoma.

METHODS: All patients were treated for glioblastoma with surgery, concomitant radiotherapy and temozolomide, and adjuvant temozolomide. Hippocampi were retrospectively delineated on three MRIs, performed at baseline, at the time of relapse, and on the last MRI available at the end of follow-up. A total of 98, 96, and 82 hippocampi were measured in the 49 patients included in the study, respectively. The patients were stratified into three subgroups according to the dose delivered to 40% of the hippocampus. In the group 1 (n = 6), the hippocampal D_40% was < 7.4 Gy, in the group 2 (n = 13), only the H_contra D_40% was < 7.4 Gy, and in the group 3 (n = 30), the D_40% for both hippocampi was > 7.4 Gy.

RESULTS: Regardless of the time of measurement, homolateral hippocampal volumes were significantly lower than those contralateral to the tumor. Regardless of the side, the volumes at the last MRI were significantly lower than those measured at baseline. There was a significant correlation among the decrease in hippocampal volume regardless of its side, and D_max (p = 0.001), D_98% (p = 0.028) and D_40% (p = 0.0002). After adjustment for the time of MRI, these correlations remained significant. According to the D_40% and volume at MRI_last, the hippocampi decreased by 4 mm³/Gy overall.

CONCLUSIONS: There was a significant relationship between the radiotherapy dose and decrease in hippocampal volume. However, at the lowest doses, the hippocampi seem to exhibit an adaptive increase in their volume, which could indicate a plasticity effect. Consequently, shielding at least one hippocampus by delivering the lowest possible dose is recommended so that cognitive function can be preserved. Trial registration Retrospectively registered.

PMID:34158078 | DOI:10.1186/s13014-021-01835-0

Zhongguo Fei Ai Za Zhi. 2021 Jun 20;24(6):426-433. doi: 10.3779/j.issn.1009-3419.2021.102.20.

ABSTRACT

BACKGROUND: Solitary pulmonary nodule has received increasing attention in recent years. A couple of lung nodules have been recognized as primary malignant tumors, which leads to an urgent need in enhancing the diagnosis of benign/malignant lung nodules at clinical settings. This study aims to explore the value of the combined detection of cytokines and tumor markers in differencing benign and malignant solitary pulmonary nodules in diagnose.

METHODS: With 81 solitary pulmonary nodules cases with a clear diagnosis, the general clinical data, nodule imaging features, pathological diagnosis data, serological index cytokine series and tumor marker expression levels were collected in groups. Both single factor and multi-factors analysis were conducted to screen out the serum influence indexes that can predict the malignant probability of lung nodules, and mean while binary logistic regression analysis was used to construct joint indexes; After receiver operating characteristic curve (ROC) was drawn, the area under the curve and the corresponding sensitivity, specificity and positive of each index predicted value, negative predicted value and accuracy could be calculated with a view to determine the statistical significance of area under the curve (AUC).

RESULTS: There are differences in the distribution of malignant solitary pulmonary nodules at different locations, with the highest proportion of the right upper lobe (40.4%). The serum levels of carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA21-1), interleukin-6 (IL-6), interleukin-8 (IL-8) in the malignant nodule group were higher than those in the benign nodule group. Logistic regression analysis suggests that CEA, IL-6 and IL-8 are independent risk factors for predicting malignant nodules. ROC curve analysis shows that the areas under the curve of the individual indicators CEA, IL-6 and IL-8 are 0.642, 0.684 and 0.749. The comparison result of the test efficiency of the area under the curve suggests that CEA+IL-6+IL-8 has a larger area under the curve and higher detection efficiency.

CONCLUSIONS: CEA, IL-6 and IL-8 are independent risk factors for malignant solitary pulmonary nodules. The combined detection of cytokines and tumor markers has played a role in the differential diagnosis of benign and malignant lung nodules. The diagnostic value of the combined detection of CEA+IL-6+IL-8 is the highest.

PMID:34157802 | DOI:10.3779/j.issn.1009-3419.2021.102.20