Work-Related Musculoskeletal Disorders: A Systematic Review and Meta-Analysis.

Background: Musculoskeletal disorders (MSDs) involve muscles, nerves, tendons, joints, cartilage, and spinal discs. These conditions can be triggered by both the work environment and the type of work performed, factors that, in some cases, can also exacerbate pre-existing conditions. This systematic review aims to provide an overview of the impact that different work-related activities have on the musculoskeletal system. Methods: A global search of publications was conducted using the following international bibliographic web databases: PubMed and Web of Science. The search strategies combined terms for musculoskeletal disorders and workers. In addition, a meta-analysis was conducted to estimate the prevalence of MSDs within the healthcare sector. Results: A total of 10,805 non-duplicated articles were identified, and finally, 32 studies were reviewed in this article. Once the literature search was completed, occupational figures were categorized into healthcare, farming, industrial, and computer sectors. In the healthcare sector, the prevalence estimate for degenerative diseases of the lumbar spine was 21% (497 out of 2547 physicians and dentists) (95% CI, 17-26%), while for osteoarthritis of the hand, it was 37% (382 out of 1013 dentists) (95% CI, 23-51%). Conclusions: Musculoskeletal disorders significantly impair workers' quality of life, especially in healthcare sector. These conditions are also associated with high costs for employers, such as absenteeism, lost productivity, and increased costs for healthcare, disability, and workers' compensation.

Repurposing Hsp90 inhibitors as antimicrobials targeting two-component systems identifies compounds leading to loss of bacterial membrane integrity.

The discovery of antimicrobials with novel mechanisms of action is crucial to tackle the foreseen global health crisis due to antimicrobial resistance. Bacterial two-component signaling systems (TCSs) are attractive targets for the discovery of novel antibacterial agents. TCS-encoding genes are found in all bacterial genomes and typically consist of a sensor histidine kinase (HK) and a response regulator. Due to the conserved Bergerat fold in the ATP-binding domain of the TCS HK and the human chaperone Hsp90, there has been much interest in repurposing inhibitors of Hsp90 as antibacterial compounds. In this study, we explore the chemical space of the known Hsp90 inhibitor scaffold 3,4-diphenylpyrazole (DPP), building on previous literature to further understand their potential for HK inhibition. Six DPP analogs inhibited HK autophosphorylation in vitro and had good antimicrobial activity against Gram-positive bacteria. However, mechanistic studies showed that their antimicrobial activity was related to damage of bacterial membranes. In addition, DPP analogs were cytotoxic to human embryonic kidney cell lines and induced the cell arrest phenotype shown for other Hsp90 inhibitors. We conclude that these DPP structures can be further optimized as specific disruptors of bacterial membranes providing binding to Hsp90 and cytotoxicity are lowered. Moreover, the X-ray crystal structure of resorcinol, a substructure of the DPP derivatives, bound to the HK CheA represents a promising starting point for the fragment-based design of novel HK inhibitors. IMPORTANCE: The discovery of novel antimicrobials is of paramount importance in tackling the imminent global health crisis of antimicrobial resistance. The discovery of novel antimicrobials with novel mechanisms of actions, e.g., targeting bacterial two-component signaling systems, is crucial to bypass existing resistance mechanisms and stimulate pharmaceutical innovations. Here, we explore the possible repurposing of compounds developed in cancer research as inhibitors of two-component systems and investigate their off-target effects such as bacterial membrane disruption and toxicity. These results highlight compounds that are promising for further development of novel bacterial membrane disruptors and two-component system inhibitors.

Metals accumulation affects bone and muscle in osteoporotic patients: A pilot study.

Osteoporosis is the most common bone disease, characterized by decreased bone mineral density (BMD) and often associated to decreased muscle mass and function. Metal exposure plays a role in the pathophysiology of osteoporosis and affects also muscle quality. The aim of this study was to assess the association between metal levels in bone and muscle samples and the degeneration of these tissues. A total of 58 subjects (30 male and 28 female) was enrolled and classified in osteoporotic (OP, n = 8), osteopenic (Ope, n = 30) and healthy (CTR, n = 20) subjects, according to BMD measures. Femoral head bone samples and vastus lateralis muscle samples were collected during hip arthroplasty surgeries. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis showed increased levels of Al, Cd and Pb in OP and Ope bone tissue compared to CTR subjects (p = 0.04, p = 0.005 and p = 0.01, respectively). Whereas, increased levels of Co, Cd and Pb were measured in OP and Ope muscle tissues, compared to CTRs (p < 0.001, p = 0.02 and p = 0.01, respectively). In addition, Al, Cd and Pb levels in bone and Cd and Co levels in muscle were negatively correlated with BMD. A negative association among Co, Cd, Cr and Hg levels and muscle fibers diameter was also observed in muscle tissues. This study assessed that metal exposure can affects bone and muscle tissue quality and may contribute to the onset and progression of musculoskeletal diseases such as osteoporosis. Therefore, it is important to implement metal exposure assessment and their impact on disease development, in order to manage and prevent metal accumulation effects on bone and muscle quality.

Prone Positioning in Postoperative Cardiac Surgery Patients: A Narrative Review.

Limited data are available on the use of the prone position in cardiac surgery. Concerns in performing this maneuver in open cardiac surgery due to the risk of post-sternotomy wound infections and hemodynamic instability do not seem to be supported by existing evidence. Indeed, available data show that prone positioning may improve gas exchange in cardiac surgery patients as well. However, previous studies of prone positioning in this setting were heterogeneous in patient characteristics and outcomes evaluated. As a result, whether prone positioning also may be effective in reducing mortality in patients with postoperative acute respiratory failure, particularly in those who underwent surgery under extracorporeal circulation, remains to be clearly elucidated. The aim of this article is to provide an overview of available literature, which seems to suggest the efficacy of prone positioning, and to make an in-depth analysis of the studies on this topic by evaluating the efficacy of this maneuver on hard endpoints.

T-Score and Handgrip Strength Association for the Diagnosis of Osteosarcopenia: A Systematic Review and Meta-Analysis.

BACKGROUND: Osteosarcopenia is a recently identified condition caused by the coexistence of osteoporosis and sarcopenia that affects the frail elderly population, leading to an increased risk of falls and fractures. Given the recent socio-economic interest associated with osteosarcopenia, the aim of this meta-analysis is to provide an overview of the factors potentially involved in its pathogenesis, assessing its population type, prevalence, and associated variables. METHODS: A comprehensive systematic search for relevant studies, published from 2015 to 2020, was performed by using PubMed, EMBASE, and Cochrane databases. We analysed the variables of age, vitamin D, handgrip, and T-score in four different groups: healthy, osteopenic-osteoporotic, sarcopenic, and osteosarcopenic. RESULTS: A total of 6504 patients from 16 studies were included in the final meta-analysis. The analysis of the individual variables reveals a statistically significant correlation between the handgrip test data and T-score (p < 0.001). CONCLUSIONS: The correlation between T-score values and handgrip strength suggests a new potential parameter in the development of predictive models that could be used in clinical practice, highlighting its importance for the diagnosis of osteosarcopenia.

Lessons learnt from the variation across 6741 family/general practices in England in the use of treatments for hypogonadism.

INTRODUCTION: We have previously reported rates of diagnosis of male hypogonadism in United Kingdom (UK) general practices. We aimed to identify factors associated with testosterone prescribing in UK general practice. METHODS: We determined for 6741 general practices in England, the level of testosterone prescribing in men and the relation between volume of testosterone prescribing and (1) demographic characteristics of the practice, (2) % patients with specific comorbidities and (3) national GP patient survey results. RESULTS: The largest volume (by prescribing volume) agents were injectable preparations at a total cost in the 12-month period 2018/19 of £8,172,519 with gel preparations in second place: total cost £4,795,057. Transdermal patches, once the only alternative to testosterone injections or implants, were little prescribed: total cost £222,022. The analysis accounted for 0.27 of the variance in testosterone prescribing between general practices. Thus, most of this variance was not accounted for by the analysis. There was a strong univariant relation (r = .95, P < .001) between PDE5-I prescribing and testosterone prescribing. Other multivariant factors independently linked with more testosterone prescribing were as follows: HIGHER proportion of men with type 2 diabetes(T2DM) on target control (HbA1c ≤ 58 mmol/mol) and HIGHER overall practice rating on the National Patient Survey for good experience, while non-white ethnicity and socio-economic deprivation were associated with less testosterone prescribing. There were a number of comorbidity factors associated with less prescribing of testosterone (such as T2DM, hypertension and stroke/TIA). CONCLUSION: Our analysis has indicated that variation between general practices in testosterone prescribing in a well developed health economy is only related to small degree (r2  = 0.27) to factors that we can define. This suggests that variation in amount of testosterone prescribed is largely related to general practitioner choice/other factors not studied and may be amenable to measures to increase knowledge/awareness of male hypogonadism, with implications for men's health.

The treatment rate of erectile dysfunction (ED) in younger men with type 2 diabetes is up to four times higher than the equivalent non-diabetes population.

INTRODUCTION: Erectile dysfunction (ED) is common in older age and in diabetes mellitus (DM). Phosphodiesterase type 5-inhibitors (PDE5-is) are the first-line for ED. We investigated how the type of diabetes and age of males affect the PDE5-i use in the primary care setting. METHODS: From 2018 to 2019, the general practice level quantity of all PDE5-i agents was taken from the general practice (GP) Prescribing Dataset in England. The variation in outcomes across practices was examined across one year, and for the same practice against the previous year. RESULTS: We included 5761 larger practices supporting 25.8 million men of whom 4.2 million ≥65 years old. Of these, 1.4 million had T2DM, with 0.8 million of these >65. About 137 000 people had T1DM. About 28.8 million tablets of PDE5-i were prescribed within the 12 months (2018-2019) period in 3.7 million prescriptions (7.7 tablets/prescription), at total costs of £15.8 million (£0.55/tablet). The NHS ED limit of one tablet/user/wk suggests that 540 000 males are being prescribed a PDE5-i at a cost of £29/y each. With approximately 30 000 GPs practising, this is equivalent to one GP providing 2.5 prescriptions/wk to overall 18 males. There was a 3x variation between the highest decile of practices (2.6 tablets/male/y) and lowest decile (0.96 tablets/male/y). The statistical model captured 14% of this variation and showed that T1DM males were the largest users, while men age <65 with T2DM were being prescribed four times as much as non-DM. Those T2DM >65 were prescribed 80% of the non-DM amount. CONCLUSION: There is a wide variation in the use of PDE5-is. With only 14% variance capture, other factors including wide variation in patient awareness, prescribing rules of local health providers, and recognition of the importance of male sexual health by GP prescribers might have a significant impact.

Dynamic bedside assessment of the physiologic effects of prone position in acute respiratory distress syndrome patients by electrical impedance tomography.

BACKGROUND: Prone position (PP) improves acute respiratory distress syndrome (ARDS) survival by reducing the risk of ventilation-induced lung injury. However, inter-individual variability is a hallmark of ARDS and lung protection by PP might not be optimal in all patients. In the present study, we dynamically assessed physiologic effects of PP by electrical impedance tomography (EIT) and identified predictors of improved lung protection by PP in ARDS patients. METHODS: Prospective physiologic study on 16 intubated, sedated and paralyzed patients with ARDS undergoing PP as per clinical decision. EIT data were recorded during two consecutive steps: 1) baseline supine position before and after a recruitment maneuver (RM); 2) prone position before and after a RM. "Improved lung protection" by PP was defined in the presence of simultaneous improvement of ventilation homogeneity (Hom), alveolar overdistension and collapse (ODCL) and amount of recruitable lung volume by RM in comparison to supine. RESULTS: PP versus supine increased the tidal volume distending the dependent regions (Vtdep), resulting in improved Hom (1.1±0.9 vs. 1.7±0.9, P=0.021). PP also reduced ODCL (19±9% vs. 28±8%, P=0.005) and increased the recruitable lung volume (80 [71-157] vs. 59 [1-110] mL, P=0.025). "Improved lung protection" by PP was predicted by lower Vtdep, higher Vtndep and poorer Hom measured during baseline supine position (P<0.05). CONCLUSIONS: EIT enables dynamic bedside assessment of the physiologic effects of PP and might support early recognition of ARDS patients more likely to benefit from PP.

Spontaneous Breathing Patterns During Maximum Extracorporeal CO2 Removal in Subjects With Early Severe ARDS.

BACKGROUND: Switching patients affected by early severe ARDS and undergoing extracorporeal membrane oxygenation (ECMO) from controlled ventilation to spontaneous breathing can be either beneficial or harmful, depending on how effectively the breathing pattern is controlled with ECMO. Identifying the factors associated with ineffective control of spontaneous breathing with ECMO may advance our pathophysiologic understanding of this syndrome. METHODS: We conducted a prospective study in subjects with severe ARDS who were on ECMO support ≤ 7 d. Subjects were switched to minimal sedation and pressure-support ventilation while extracorporeal CO2 removal was increased to approximate the subject's total CO2 production ([Formula: see text]). We calculated the rapid shallow breathing index (RSBI) as breathing frequency divided by tidal volume. We explored the correlation between certain characteristics recorded during pretest controlled ventilation and the development of apnea (ie, expiratory pause lasting > 10 s; n = 3), normal breathing pattern (ie, apnea to RSBI ≤ 105 breaths/min/L; n = 6), and rapid shallow breathing (RSBI > 105 breaths/min/L; n = 6) that occurred during the test study. RESULTS: The ratio of extracorporeal CO2 removal to the subjects' [Formula: see text] was >90% in all 15 subjects, and arterial blood gases remained within normal ranges. Baseline pretest Sequential Organ Failure Assessment score, total [Formula: see text] and ventilatory ratio increased steadily, whereas [Formula: see text]/[Formula: see text] was higher in subjects with apnea compared to intermediate RSBI ≤105 breaths/min/L and elevated RSBI >105 breaths/min/L. In subjects with rapid shallow breathing, baseline lung weight measured with quantitative computed tomography scored higher, as well. CONCLUSIONS: In early severe ARDS, the factors associated with rapid shallow breathing despite maximum extracorporeal CO2 extraction include less efficient CO2 and O2 exchange by the natural lung, higher severity of organ failure, and greater magnitude of lung edema.

Noninvasive assessment of airflows by electrical impedance tomography in intubated hypoxemic patients: an exploratory study.

BACKGROUND: Noninvasive monitoring of maximal inspiratory and expiratory flows (MIF and MEF, respectively) by electrical impedance tomography (EIT) might enable early recognition of changes in the mechanical properties of the respiratory system due to new conditions or in response to treatments. We aimed to validate EIT-based measures of MIF and MEF against spirometry in intubated hypoxemic patients during controlled ventilation and spontaneous breathing. Moreover, regional distribution of maximal airflows might interact with lung pathology and increase the risk of additional ventilation injury. Thus, we also aimed to describe the effects of mechanical ventilation settings on regional MIF and MEF. METHODS: We performed a new analysis of data from two prospective, randomized, crossover studies. We included intubated patients admitted to the intensive care unit with acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS) undergoing pressure support ventilation (PSV, n = 10) and volume-controlled ventilation (VCV, n = 20). We measured MIF and MEF by spirometry and EIT during six different combinations of ventilation settings: higher vs. lower support during PSV and higher vs. lower positive end-expiratory pressure (PEEP) during both PSV and VCV. Regional airflows were assessed by EIT in dependent and non-dependent lung regions, too. RESULTS: MIF and MEF measured by EIT were tightly correlated with those measured by spirometry during all conditions (range of R2 0.629-0.776 and R2 0.606-0.772, respectively, p < 0.05 for all), with clinically acceptable limits of agreement. Higher PEEP significantly improved homogeneity in the regional distribution of MIF and MEF during volume-controlled ventilation, by increasing airflows in the dependent lung regions and lowering them in the non-dependent ones. CONCLUSIONS: EIT provides accurate noninvasive monitoring of MIF and MEF. The present study also generates the hypothesis that EIT could guide PSV and PEEP settings aimed to increase homogeneity of distending and deflating regional airflows.

In-hospital major arrhythmias, arrhythmic death and resuscitation after successful primary percutaneous intervention for acute transmural infarction: a retrospective single-centre cohort study.

BACKGROUND: Transmural acute myocardial infarction (AMI) is associated with a high risk for ventricular arrhythmia before, during and after treatment. Consequently, it is recommended that patients diagnosed with transmural AMI be monitored in a cardiac care unit (CCU) so life-threatening arrhythmias can be treated promptly. We examined the incidence and timing of in-hospital malignant ventricular arrhythmias, sudden cardiac or arrhythmic death (SCD/AD) and resuscitation requirements in patients with transmural AMI recovering from percutaneous coronary intervention (PCI) undertaken within 12 h of symptom onset and without antecedent thrombolysis. METHODS: This was a retrospective cohort study using the Duisburg Heart Center (Germany) cardiac patient registry. In total, 975 patients met the inclusion criteria. The composite endpoint was post-PCI ventricular fibrillation or tachycardia, SCD/AD or requirement for resuscitation. We compared the demographic and clinical characteristics of patients who met the composite endpoint with those who did not, recorded the timing of endpoint episodes, and used multivariable logistic regression analysis to identify factors associated with the endpoint criteria. RESULTS: There was no significant difference in the length of CCU or hospital stay between the groups. In-hospital mortality was 6.5%, and the composite endpoint was met in 7.4% of cases. Malignant ventricular tachyarrhythmia occurred in 2.8% of the patients, and SCD/AD occurred in 0.3% of the cases. There was a biphasic temporal distribution of endpoint events; specifically, 76.7% occurred < 96 h after symptom onset, and 12.6% occurred 240-360 h after symptom onset. Multivariable regression analysis identified positive associations between an endpoint episode and the following: age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05] per year); left ventricular ejection fraction (LVEF) < 30% (OR 3.66, 95% CI 1.91-6.99); peak serum creatine phosphokinase concentration (OR 1.01, 95% CI 1.00-1.02 per 100 U/dl); leucocytosis (OR 1.86, 95% CI 1.04-3.32), and coronary thrombus (OR 1.85, 95% CI 1.04-3.27). CONCLUSIONS: Most post-PCI malignant ventricular arrhythmias, SCD/AD and resuscitation episodes occurred within 96 h of transmural AMI (76.7%). A substantial minority (12.6%) of these events arose 240-360 h after symptom onset. Further study is needed to establish the influence of age, LVEF < 30%, peak serum creatine phosphokinase concentration, leucocytosis and coronary thrombus on post-PCI outcomes after transmural AMI.

Open Abdomen Management and Candida Infections: A Very Likely Link.

OBJECTIVE: Laparostomy can be applied in trauma, abdominal sepsis, intra-abdominal hypertension, or compartment syndrome. Systemic infections, especially if complicated by Candida, are associated with a high risk of mortality. METHODS: This is a single-centre retrospective case series of 47 cases admitted to our Department, which required laparostomy procedure; we analyzed the type of surgery, temporary abdominal closure, duration of open abdomen, complications, SOFA score, mortality with Candida infections, and empirical or targeted antifungal therapy. RESULTS: We found that patients with Candida infection were related with a statistically significant difference (p < 0.05) with a complication after OA closure, total complications, time elapsed after OA application, time spent on the first surgical OA application, type of temporary abdominal closure that is used, and duration of the open abdomen. The use of empirical and targeted antifungal therapy is related to the duration of open abdomen too. CONCLUSIONS: Management of the OA is often burdened by sepsis or septic shock, especially when complicated by Candida infection. Candida score is a validated tool to identify patients who can be treated empirically, but every situation must be considered on an individual basis.

Evaluation of heart rate measurements in clinical studies: a prospective cohort study in patients with heart disease.

PURPOSE: The purpose of this study was to evaluate the measurement of heart rate undertaken in clinical studies by (1) assessing the repeatability and reproducibility of heart rate measurements by various methods and under various conditions and (2) determining whether a single heart rate measurement at rest is representative of the circadian and inter-day variation of heart rate. METHODS: Prospective cohort study in 102 patients with various types of heart disease at Duisburg Heart Center, Germany between 2011 and 2012. The heart rate measurements were based on self-assessment, ECG tracings at rest, and bicycle stress ECG in the office as well as 24-h Holter ECG. RESULTS: Office measurements and self-assessment at rest as well as 24-h Holter ECG and self-assessment at rest are highly correlated, but no correlation between self-assessment and office recordings/24 h recordings under exercise conditions was seen. Coefficient of variability was below 10 % for the self-assessment and for office measurements at rest. There were no differences in coefficient of variability during the day and within the 6 days for self-assessment of heart rate at rest and circadian variation was normal. CONCLUSIONS: At rest heart rate measurements by various methods agree sufficiently and inter-day/circadian variation is adequately represented. Under exercise conditions self-assessment of heart rate is not valuable and use of 24 h Holter as well as stress ECG recordings is necessary. Thus, self-reported heart rate measurements by the patient at rest seem to be reliable, but should be used in clinical studies only for heart rate assessment at rest.