Adherence to protective mechanical ventilation in COVID-19 versus non-COVID-19-associated acute respiratory distress syndrome: Comparison between two prospective cohorts / Adhesión a la ventilación mecánica protectora en el síndrome de dificultad respiratoria aguda asociado a COVID-19 o asociado a otras etiologias: comparación entre dos cohortes prospectivas

Objective To compare adherence to protective mechanical ventilation (MV) parametersin patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 with patients with ARDS from other etiologies. Design Multiple prospective cohort study. Setting: Two Brazilian cohorts of ARDS patients were evaluated. One with COVID-19 patients admitted to two Brazilian intensive care units (ICUs) in 2020 and 2021 (C-ARDS, n=282), the other with ARDS-patients from other etiologies admitted to 37 Brazilian ICUs in 2016 (NC-ARDS, n=120). Patients: ARDS patients under MV. Interventions: None. Main variables of interest: Adherence to protective MV (tidal volume ≤8mL/kg PBW; plateau pressure ≤30cmH2O; and driving pressure ≤15cmH2O), adherence to each individual component of the protective MV, and the association between protective MV and mortality. Results Adherence to protective MV was higher in C-ARDS than in NC-ARDS patients (65.8% vs. 50.0%, p=0.005), mainly due to a higher adherence to driving pressure ≤15cmH2O (75.0% vs. 62.4%, p=0.02). Multivariable logistic regression showed that the C-ARDS cohort was independently associated with adherence to protective MV. Among the components of the protective MV, only limiting driving pressure was independently associated with lower ICU mortality. Conclusions Higher adherence to protective MV in patients with C-ARDS was secondary to higher adherence to limiting driving pressure. Additionally, lower driving pressure was independently associated with lower ICU mortality, which suggests that limiting exposure to driving pressure may improve survival in these patients (AU)

Objetivo Comparar la adhesión a la ventilación mecánica (VM) protectora en pacientes con síndrome de dificultad respiratoria aguda (SDRA) causada por COVID-19 con pacientes con SDRA de otras etiologías. Diseño Estudio de cohorte prospectivo. Âmbito: Se evaluaron dos cohortes de pacientes con SDRA: 1.pacientes con COVID-19 ingresados en dos unidades de cuidados intensivos (UCI) brasileñas en 2020 y 2021 (C-ARDS, n=282); 2.pacientes con SDRA de otras etiologías ingresados en 37 UCI brasileñas en 2016 (NC-ARDS, n=120). Pacientes: Pacientes con SDRA bajo VM invasiva. Intervenciones: No. Variables de interés principals: Adhesión a la VM protectora (volumen tidal ≤8mL/kg; presión de meseta ≤30cmH2O; y presión de distensión [PD] ≤15cmH2O), adhesión a cada componente individual de la VM protectora, y la asociación entre la VM protectora y la mortalidad. Resultados La adhesión a la VM protectora fue mayor en la cohorte C-ARDS que en la NC-ARDS (65,8% vs. 50,0%, p=0,005), principalmente debido a mayor adhesión a la PD≤15cmH2O (75,0% vs. 62,4%, p=0,02). La regresión logística multivariable mostró que la cohorte C-ARDS se asoció de forma independiente con la adhesión a la VM protectora. Entre los componentes de la VM protectora, sólo la limitación de la PD se asoció de forma independiente con menor mortalidad en la UCI. Conclusión La mayor adhesión a la VM protectora en los pacientes con C-ARDS fue secundaria a la mayor adhesión a limitación da PD. Además, una menor PD se asoció de forma independiente a menor mortalidad en la UCI, lo que sugiere que limitar la exposición a altas PD puede mejorar la supervivencia en estos pacientes (AU)

Adherence to protective mechanical ventilation in COVID-19 versus non-COVID-19-associated acute respiratory distress syndrome: Comparison between two prospective cohorts.

OBJECTIVE: To compare adherence to protective mechanical ventilation (MV) parameters in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 with patients with ARDS from other etiologies. DESIGN: Multiple prospective cohort study. SETTING: Two Brazilian cohorts of ARDS patients were evaluated. One with COVID-19 patients admitted to two Brazilian intensive care units (ICUs) in 2020 and 2021 (C-ARDS, n=282), the other with ARDS-patients from other etiologies admitted to 37 Brazilian ICUs in 2016 (NC-ARDS, n=120). PATIENTS: ARDS patients under MV. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Adherence to protective MV (tidal volume ≤8mL/kg PBW; plateau pressure ≤30cmH2O; and driving pressure ≤15cmH2O), adherence to each individual component of the protective MV, and the association between protective MV and mortality. RESULTS: Adherence to protective MV was higher in C-ARDS than in NC-ARDS patients (65.8% vs. 50.0%, p=0.005), mainly due to a higher adherence to driving pressure ≤15cmH2O (75.0% vs. 62.4%, p=0.02). Multivariable logistic regression showed that the C-ARDS cohort was independently associated with adherence to protective MV. Among the components of the protective MV, only limiting driving pressure was independently associated with lower ICU mortality. CONCLUSIONS: Higher adherence to protective MV in patients with C-ARDS was secondary to higher adherence to limiting driving pressure. Additionally, lower driving pressure was independently associated with lower ICU mortality, which suggests that limiting exposure to driving pressure may improve survival in these patients.

Trends in Scope of Practice for Oral Health Care: Future Transformative Effects.

KNOWLEDGE TRANSFER STATEMENT: The results of this study can help key stakeholders, such as health care facilities, educational and research institutions, insurance companies, and governmental bodies, plan future activities and policies on dental practice and education.

µ-Opioid Activity in Chronic TMD Pain Is Associated with COMT Polymorphism.

Clinicians have the dilemma of prescribing opioid or nonopioid analgesics to chronic pain patients; however, the impact of pain on our endogenous µ-opioid system and how our genetic profile (specifically catechol-O-methyltransferase [COMT] polymorphisms) impacts its activation are currently unknown. Twelve chronic temporomandibular disorder (TMD) patients and 12 healthy controls (HCs) were scanned using positron emission tomography (PET) with [11C]carfentanil, a selective radioligand for µ-opioid receptors (µORs). The first 45 min of each PET measured the µOR nondisplaceable binding potential (BPND) at resting state, and the last 45 min consisted of a 20-min masseteric pain challenge with an injection of 5% hypertonic saline. Participants were also genotyped for different COMT alleles. There were no group differences in µOR BPND at resting state (early phase). However, during the masseteric pain challenge (late phase), TMD patients exhibited significant reductions in µOR BPND (decreased [11C]carfentanil binding) in the contralateral parahippocampus (P = 0.002) compared to HCs. The µOR BPND was also significantly lower in TMD patients with longer pain chronicity (P < 0.001). When considering COMT genotype and chronic pain suffering, TMD patients with the COMT158Met substitution had higher pain sensitivity and longer pain chronicity with a 5-y threshold for µOR BPND changes to occur in the parahippocampus. Together, the TMD diagnosis, COMT158Met substitution, and pain chronicity explained 52% of µOR BPND variance in the parahippocampus (cumulative R2 = 52%, P < 0.003, and HC vs. TMD Cohen's effect size d = 1.33 SD). There is strong evidence of dysregulation of our main analgesic and limbic systems in chronic TMD pain. The data also support precision medicine by helping identify TMD patients who may be more susceptible to chronic pain sensitivity and opioid dysfunction based on their genetic profile.

FAAH selectively influences placebo effects.

Endogenous opioid and cannabinoid systems are thought to act synergistically regulating antinociceptive and reward mechanisms. To further understand the human implications of the interaction between these two systems, we investigated the role of the common, functional missense variant Pro129Thr of the gene coding fatty acid amide hydrolase (FAAH), the major degrading enzyme of endocannabinoids, on psychophysical and neurotransmitter (dopaminergic, opioid) responses to pain and placebo-induced analgesia in humans. FAAH Pro129/Pro129 homozygotes, who constitute nearly half of the population, reported higher placebo analgesia and more positive affective states immediately and 24 h after placebo administration; no effects on pain report in the absence of placebo were observed. Pro129/Pro129 homozygotes also showed greater placebo-induced µ-opioid, but not D(2/3) dopaminergic, enhancements in neurotransmission in regions known involved in placebo effects. These results show that a common genetic variation affecting the function of the cannabinoid system is serving as a probe to demonstrate the involvement of cannabinoid and opioid transmitters on the formation of placebo effects.

Servo-controlled stepped and ramped mechanical tissue algometry.

A hand-held, servo-controlled tissue palpation device (SCPD) was developed to measure the pressure-pain characteristics of human tissue for disease states linked to altered pressure-pain sensitivity. The design was based on an adaptive controller using force feedback to reach and maintain a desired force in spite of movements of the operator's hand holding the device or positional changes of the subject.

Regional mu opioid receptor regulation of sensory and affective dimensions of pain.

The endogenous opioid system is involved in stress responses, in the regulation of the experience of pain, and in the action of analgesic opiate drugs. We examined the function of the opioid system and mu-opioid receptors in the brains of healthy human subjects undergoing sustained pain. Sustained pain induced the regional release of endogenous opioids interacting with mu-opioid receptors in a number of cortical and subcortical brain regions. The activation of the mu-opioid receptor system was associated with reductions in the sensory and affective ratings of the pain experience, with distinct neuroanatomical involvements. These data demonstrate the central role of the mu-opioid receptors and their endogenous ligands in the regulation of sensory and affective components of the pain experience.

Habituation of the early pain-specific respiratory response in sustained pain.

Neurokinin-1 receptor and mu-opioid receptor agonists affect respiratory rhythm when injected directly into the preBötzinger brainstem complex, which is the hypothesized site for respiratory rhythmogenesis in mammals (Science 286 (1999) 1566). Early stress-induced analgesia (SIA) is naloxone-insensitive and as such considered independent of the activation of the mu-opioid system. Prolonged application of electrical shocks, however, produces analgesia that is mediated by the mu-opioid system (Science 208 (1980) 623). Together these findings suggest that any early pain-specific increased respiration should be attenuated in the tonic state of pain. Ten healthy, pain-free female volunteer subjects participated in this experimental study involving deep acute and tonic pain. The experimental design included three conditions: (1) baseline; (2) pain; and (3) a placebo control stimulus. Experimental pain was induced by the infusion of hypertonic saline into the masseter muscle. Infusion of isotonic saline in the contralateral masseter was used as a control. Blinded subjects were randomly assigned to a particular sequential order of the experimental stages, i.e. hypertonic saline infusion preceded the isotonic saline infusion or vice versa. Respiration rate, mean peak inspiratory and expiratory flow rates, and the minute ventilation volume quantified breathing. Results indicate that effects on respiration were pain-specific and that the early effects on respiration were significantly attenuated in sustained pain. In the early stage of pain, all monitored variables (respiration rate, minute ventilation volume, and inspiratory and expiratory flow rates) were elevated to statistically significant degrees when compared to measurements taken at baseline or during control infusion. Only respiration rate continued to be significantly elevated in sustained pain. We concluded that rhythmogenic neurons in the preBötzinger brainstem complex appear as the likely target for pro-nociceptive and anti-nociceptive input, explaining both the observed initial facilitation and subsequent habituation of respiration in early and sustained pain.

Chronic orofacial pain: is the puzzle unraveling?

Conditions involving chronic orofacial pain represent a major health problem, and patients with persistent pain are difficult to manage successfully. These conditions are often comorbid with additional health issues such as sleep disturbances, cardiovascular, gastrointestinal and reproductive system complaints, weight loss or weight gain, swelling, numbness, sweating and flushing, and concerns regarding loss of libido, drive, attention, and memory. Neuroendocrine and autonomic pain-stress responsivity and the consequences of pain for sensory, motor, immune and reproductive functions, and mood seem to account for the broad range of comorbid complaints. Susceptibility to a particular response appears to explain intra-individual differences in disease expression. Understanding of these regulatory, mostly adaptive processes will support novel treatments to manage many troublesome comorbid complaints for which current approaches are unsatisfactory.

The effect of bolus size on the chewing cycle in humans.

No general agreement exists regarding the effect that bolus size has on masticatory movement, probably because both the size and texture of food change during mastication. In this experiment, in order to clarify the effect of bolus size on masticatory movement, a food that does not change in size and texture--chewing gum--was chosen, and the relationship between bolus size and the chewing cycle was analyzed. Ten healthy subjects in their twenties were asked to chew pieces of softened chewing gum of four different sizes. For ten cycles, beginning with the fifth cycle of mastication, gape and masticatory width were calculated for the spatial parameter of the chewing cycle, and cycle time was calculated as the temporal parameter. The relationship between these parameters and the bolus size was investigated. As the bolus size increased, the spatial and temporal parameters increased. In addition, there was a positive correlation between the bolus size and each parameter. The influence of the bolus size was as follows: gape, r = 0.91; masticatory width, r = 0.79; and cycle time, r = 0.74 (all, P < 0.001). From these results it was concluded that the shape of the chewing cycle was altered by the size of the food bolus, and that the changes in sensory input from the peripheries greatly affected the masticatory movement.

Generic pain intensity scores are affected by painful comorbidity.

AIMS: To determine the degree to which the generic pain intensity rating (i.e., overall and without reference to a particular body site) of facial pain patients being seen in a specialty setting for facial pain is influenced by painful comorbidity in body parts other than the face. METHODS: In this prospective study, 40 consecutive female temporomandibular pain patients rated their generic pain on a 100-mm visual analog scale. After marking all painful body sites on pain drawings, patients were asked to rate the pain intensity for each of the indicated pain sites; the patients did not have access to the generic pain intensity score. Pearson's correlation coefficient was used to correlate the generic pain intensity score with site-specific pain intensity ratings, their mean and maximum, and the number of pain sites. RESULTS: The medians of the generic, maximum, and facial pain intensity scores were 49.5, 53, and 45.5, respectively. The generic pain intensity rating correlated more highly with the intensity scores reported for the most painful body site (r2 = 0.82; P < 0.001) than with the average rating across all painful sites (r2 = 0.62; P < 0.001), or the pain intensity score in the face (r2 = 0.61; P < 0.001). The number of pain sites did not correlate to any statistically significant degree with the generic pain intensity rating (r2 = 0.006; P = 0.65). CONCLUSION: The results of this study suggest that the maximum visual analog scale pain intensity score, observed in any body location, is a better reflection of the generic pain intensity rating than the corresponding score of the face. To avoid over-rating or underrating of facial pain intensity, patients should be instructed to provide site-specific pain intensity scores if painful comorbidity is present.

Spatial and temporal summation of sensory and affective dimensions of deep somatic pain.

There is considerable evidence in support of differential information processing of the sensory-discriminative and motivational-affective meanings of pain. The purpose of this work was to examine whether temporal (acute, tonic, persistent) and spatial (local, regional, widespread) aspects of deep somatic pain influence the sensory and affective dimensions of pain. Acute pain consisted of a short bout of pain, lasting about 100 s. Tonic pain was the experience of experimentally maintained pain for 18 min. Both acute and tonic pain were induced by infusion of an algesic or control substance into muscle with the subject blinded with respect to the type of infusion and randomization of the application sequence. Comparing the response of experimental subjects to a group of matched cases with persistent masticatory myalgia alone or in combination with widespread musculoskeletal pain, we examine whether the experimental state is different from the matched clinical condition, and whether there is a difference between the condition being restricted to the face or not. The McGill pain questionnaire was used to assess the sensory and affective correlates of pain. The normalized sensory score for acute/unilateral face pain was different from that established for tonic/unilateral face pain (P = 0.055, borderline s.), and so was the normalized affective score (P = 0.009, s.). When comparing tonic/unilateral versus tonic/bilateral face pain, the affective scores increased with increased pain involvement (P = 0.009, s.) while the sensory sores were unaffected by the additional pain induced in the contralateral masseter muscle (P = 0.357, n.s). Notably, sensory and affective scores for tonic/bilateral and persistent/bilateral face pain were not statistically different (sensory: P = 0.169, n.s.; affective: P = 0.643, n.s). On the other hand, when contrasting persistent/bilateral face pain with persistent/ widespread musculoskeletal pain, both scores were significantly different (sensory: P < 0.001, s.; affective: P = 0.041, s.). Time in and spread of pain influenced the perceptual correlates of pain to a significant degree. The major increase in the sensory dimension occurred from 'no pain' to 'acute pain'. Affective scores showed the most significant increases from acute to tonic pain, particularly with greater spatial involvement. The significant increases in sensory scores observed when contrasting persistent facial pain alone and in combination with widespread musculoskeletal pain was attributed to the broader body experience. Because the perceptual correlates of tonic and matched persistent (chronic) pain states were similar, we concluded that it does not require months for the development of the sensory and affective meaning of persistent pain as assumed.

Craniofacial pain and motor function: pathogenesis, clinical correlates, and implications.

Many structural, behavioral, and pharmacological interventions imply that favorable treatment effects in musculoskeletal pain states are mediated through the correction of muscle function. The common theme of these interventions is captured in the popular idea that structural or psychological factors cause muscle hyperactivity, muscle overwork, muscle fatigue, and ultimately pain. Although symptoms and signs of motor dysfunction can sometimes be explained by changes in structure, there is strong evidence that they can also be caused by pain. This new understanding has resulted in a better appreciation of the pathogenesis of symptoms and signs of the musculoskeletal pain conditions, including the sequence of events that leads to the development of motor dysfunction. With the improved understanding of the relationship between pain and motor function, including the inappropriateness of many clinical assumptions, a new literature emerges that opens the door to exciting therapeutic opportunities. Novel treatments are expected to have a profound impact on the care of musculoskeletal pain and its effect on motor function in the not-too-distant future.

Treatment-seeking patterns of facial pain patients: many possibilities, limited satisfaction.

Knowledge about the different kinds of treatment provided to patients with nonmalignant musculoskeletal facial pain is limited. The present study was based on 206 consecutive patients who were referred to a university-based tertiary care clinic for the diagnosis and management of persistent facial pain. Its purpose was to get information about the number and specialty of providers consulted by patients prior to their referral, and to follow the underlying treatment-seeking patterns. The results showed that on average 4.88 providers from 44 different categories were consulted. A general dentist or a dental specialist was seen by about 70% of patients. For patients whose first provider was a dentist, the most likely subsequent provider was another dentist. Conversely, if the first provider was a physician, chances were greater that the subsequent provider was a physician rather than a dentist. Among the nondental therapies patients received, physical therapy was chosen most frequently (42.2%). More than 60% of patients had at least one nondental treatment; however, the majority of these patients experienced two or more different types of such therapy (e.g., chiropractic, osteopathic, relaxation training). Patients' satisfaction with care and treatment was moderate, since only 18.5% of the patients were very satisfied, while 27.7% were dissatisfied or very dissatisfied. The present findings, which corroborate a recent study from the Kansas City, Missouri, region, indicate that patients with persistent facial pain see a large number of different providers, and that nonmedical/nondental treatment approaches are common. The moderate satisfaction experienced with any of the therapies points out that much needs to be done before this patient population is served satisfactorily.

Pain maps from facial pain patients indicate a broad pain geography.

Two hundred consecutive female patients, who were referred to a university-based facial pain clinic, were asked to mark all painful sites on sketches showing the contours of a human body in the frontal and rear views. The drawings were analyzed with transparent templates containing 1875 (frontal view) and 1929 (rear view) square cells of equal size. The average patient scored 71.8 cells in the frontal and 99.7 cells in the rear view (corresponding to 3.8% and 5.2% of the maximum possible scores). In individual patient drawings, however, up to 42.7% and 44.9% of all cells were marked. Only 37 cases (18.5%) exhibited pain that was limited to the trigeminal system. An analysis of the pain distribution according to the arrangements of dermatomes revealed three distinct clusters of patients: (1) pain restricted to the region innervated by the trigeminal nerves (n = 37); (2) pain in the trigeminal dermatomes and any combination involving the spinal dermatomes C2, C3, and C4, but no other dermatomes (n = 32); and (3) pain sites involving dermatomes in addition to the ones listed above (n = 131). Mean ages in the three clusters were 38.7, 35.5, and 37.5 years, respectively (p = 0.62, n.s.). Widespread pain existed for longer durations (median, 48 months) than conditions involving local and regional pain (median, 24 months) (p = 0.02, s.). Our findings showed that among a great percentage of persistent facial pain patients the pain distribution is more widespread than commonly assumed, and that the persistence of pain in the regional and widespread pain presentations is significantly greater than in cases with pain limited to the trigeminal system.

Measurement of facial soft tissue mobility in man.

OBJECTIVE: The assessment of facial mobility is a key element in the treatment of patients with facial motor deficits. In this study, we explored the utility of a three-dimensional tracking system in the measurement of facial movements. METHODS AND RESULTS: First, the three-dimensional movement of potentially stable facial soft-tissue, headcap, and dental landmarks was measured with respect to a fixed space frame. Based on the assumption that the dental landmarks are stable, their motion during a series of standardized facial animations was subtracted from that of the facial and headcap landmarks to estimate their movement within the face. This residual movement was used to determine which points are relatively stable (< or = 1.5 mm of movement) and which are not (> or = 1.5 mm of movement). Headcap landmarks were found to be suitable as references during smile, cheek puff, and lip purse animations, and during talking. In contrast, skin-based landmarks were unsuitable as references because of their considerable and highly variable movement during facial animation. Second, the facial movements of patients with obvious facial deformities were compared with those of matched controls to characterize the face validity of three-dimensional tracking. In all instances, pictures that appear to be characteristic of the various functional deficits emerged. CONCLUSIONS: Our results argue that tracking instrumentation is a potentially useful tool in the measurement of facial mobility.