Structural MRI findings in the brain related to pain distribution in chronic overlapping pain conditions: An explorative case-control study in females with fibromyalgia, temporomandibular disorder-related chronic pain and pain-free controls.

BACKGROUND: Few neuroimaging studies have investigated structural brain differences associated with variations in pain distribution. OBJECTIVE: To explore structural differences of the brain in fibromyalgia (FM), temporomandibular disorder pain (TMD) and healthy pain-free controls (CON) using structural and diffusion MRI. METHODS: A case-control exploratory study with three study groups with different pain distribution were recruited: FM (n = 16; mean age [standard deviation]: 44 [14] years), TMD (n = 17, 39 [14] years) and CON (n = 10, 37 [14] years). Participants were recruited at the University Dental Clinic in Malmö, Sweden. T1-weighted and diffusion MRIs were acquired, clinical and psychosocial measures were obtained. Main outcome measures were subcortical volume, cortical thickness, white matter microstructure and whole brain grey matter intensity. RESULTS: Patients with FM had smaller volume in the right thalamus than patients with TMD (p = .020) and CON (p = .030). The right thalamus volume was negatively correlated to pain intensity (r = -0.37, p = .022) and pain-related disability (r = -0.45, p = .004). The FM group had lower cortical thickness in the right anterior prefrontal cortex than CON (p = .005). Cortical thickness in this area was negatively correlated to pain intensity (r [37] = - 0.48, p = .002). CONCLUSIONS: This study suggests that thalamus grey matter alterations are associated with FM and TMD, and that anterior prefrontal cortex grey matter alterations are associated with FM but not TMD. Studies on chronic overlapping pain conditions are needed in relation to possible nociplastic pain mechanisms in the brain and central nervous system.

Atypical mycobacterium infection following upper eyelid Müller's muscle-conjunctival resection - case report.

Periorbital non-tuberculous mycobacterium (NTM) infections are uncommon. To the best of our knowledge, NTM infection as a complication following Müller's muscle-conjunctival resection (MMCR) surgery has not been reported before. We report a case of left upper lid M. Chelonae infection following MMCR surgery. A 61-year-old lady presented with left upper lid swelling and nodular mass 4 weeks after bilateral MMCR surgery for aponeurotic ptosis. Past medical and ocular history include systemic lupus erythematosus (SLE), chronic hepatitis B infection, bilateral cataract operation done 14 years ago and right eye Fuch's dystrophy with Descemet stripping automated endothelial keratoplasty done 3 years ago. She was initially treated with topical and oral antibiotics, as well as repeated incision and curettage and intralesional steroid injection with limited improvement. Seven months post-MMCR, repeated biopsy and nodule debulking were performed. Biopsy revealed granulomatous inflammation with mycobacterial infection and PCR identified M. Chelonae. A total of 6 months course of combination systemic antibiotics were given, with good response. Limited blepharoplasty with repeat nodular excision was performed 15 months after the initial MMCR surgery, and biopsy culture and PCR were both negative. No relapse of symptoms was noted and good lid height was maintained at 30 months of follow-up. Management of periorbital NTM infections can be challenging. Clinicians should consider early diagnostic workup with mycobacterial culture and PCR in suspicious cases, followed by prompt initiation of empiric treatment with systemic macrolides. A combination of surgical excision of nodules and prolonged systemic antimicrobial treatment is needed for complete organism eradication.

Late-Onset Nontuberculous Mycobacterial Keratitis After Small Incision Lenticule Extraction.

PURPOSE: The purpose of this article was to report a case of unilateral late-onset nontuberculous mycobacterial keratitis after small incision lenticule extraction (SMILE). METHODS: This was a case report. RESULTS: A 27-year-old woman presented with Mycobacterium chelonae keratitis 3 weeks after uncomplicated SMILE with a solitary interface infiltrate. The keratitis worsened after an initial response to topical fortified and interface antibiotic irrigation. Despite repeated interface irrigation and topical and oral antibiotics, progressive, diffuse stromal infiltrates followed by melting of the cap ensued over the next 6 weeks. Cap amputation and intrastromal antibiotic injection followed by prolonged topical and oral antibiotics usage for the following 5 weeks led to infiltrate resolution and re-epithelization of the residual stromal bed. All medications were tapered off over 6 months after initial presentation without recurrence, but anterior stromal scarring and corneal neovascularization persisted. CONCLUSIONS: Cap amputation and intrastromal antibiotic injection for intractable post-SMILE keratitis can prevent the need for therapeutic keratoplasty.

Internet-Based Multimodal Pain Program With Telephone Support for Adults With Chronic Temporomandibular Disorder Pain: Randomized Controlled Pilot Trial.

BACKGROUND: Chronic pain from temporomandibular disorders remains an undertreated condition with debate regarding the most effective treatment modalities. OBJECTIVE: The aim of the study was to investigate the treatment effect of an internet-based multimodal pain program on chronic temporomandibular disorder pain and evaluate the feasibility of a larger randomized controlled trial. METHODS: An unblinded randomized controlled pilot trial was conducted with 43 participants (34 females, 9 males; median age 27, IQR 23-37 years) with chronic temporomandibular pain. Participants were recruited within the Public Dental Health Service and randomized to intervention (n=20) or active control (n=23). The intervention comprised a dentist-assisted internet-based multimodal pain program with 7 modules based on cognitive behavior therapy and self-management principles. The control group received conventional occlusal splint therapy. Primary outcomes included characteristic pain intensity, pain-related disability, and jaw functional limitation. Secondary outcomes were depression, anxiety, catastrophizing, and stress. Outcomes were self-assessed through questionnaires sent by mail at 3 and 6 months after treatment start. Feasibility evaluation included testing the study protocol and estimation of recruitment and attrition rates in the current research setting. RESULTS: Only 49% of participants (21/43) provided data at the 6-month follow-up (internet-based multimodal pain program: n=7; control: n=14). Of the 20 participants randomized to the internet-based multimodal pain program, 14 started treatment and 8 completed all 7 modules of the program. Between-group analysis showed no significant difference for any outcome measure at 3- or 6-month follow-up-characteristic pain intensity (3 months: P=.58; 6 months: P=.41), pain-related disability (3 months: P=.51; 6 months: P=.12), jaw functional limitation (3 months: P=.45; 6 months: P=.90), degree of depression (3 months: P=.64; 6 months: P=.65), anxiety (3 months: P=.93; 6 months: P=.31), stress (3 months: P=.66; 6 months: P=.74), or catastrophizing (3 months: P=.86; 6 months: P=.85). Within-group analysis in the internet-based multimodal pain program group showed a significant reduction in jaw functional limitation score at the 6-month follow-up compared to baseline (Friedman: χ2=10.2, P=.04; Wilcoxon: z=-2.3, P=.02). In the occlusal splint group, jaw function limitation was also reduced at the 6-month follow-up (Friedman: χ2=20.0, P=.045; Wilcoxon: z=-2.3, P=.02), and there was a reduction in characteristic pain intensity at the 3- and 6-month follow-up (Friedman: χ2=25.1, P=.01; Wilcoxon 3 months: z=-3.0, P=.003; Wilcoxon 6 months: z=-3.3, P=.001). CONCLUSIONS: This study was not able to demonstrate a difference in treatment outcome between an internet-based multimodal pain program and occlusal splint therapy in patients with chronic temporomandibular pain. However, the findings suggested that the internet-based multimodal pain program improves jaw function. The results also confirmed the treatment effect of occlusal splint therapy for chronic temporomandibular pain. Furthermore, because of the high attrition rate, this pilot study showed that a randomized controlled trial with this design is not feasible. TRIAL REGISTRATION: ClinicalTrials.gov NCT04363762; https://clinicaltrials.gov/show/NCT04363762.

Spectroscopic differences in posterior insula in patients with chronic temporomandibular pain.

Background and aims Chronic pain including temporomandibular disorder (TMD) pain involves a complex interplay between peripheral and central sensitization, endogenous modulatory pathways, cortical processing and integration and numerous psychological, behavioral and social factors. The aim of this study was to compare spectroscopic patterns of N-Acetyl-aspartate (NAA), total creatine (tCr), choline (Cho), myo-inositol (MI), glutamate (Glu), and the combination of Glu and glutamine in the posterior insula in patients with chronic generalized or regional chronic TMD pain (gTMD and rTMD, respectively) compared to healthy individuals (HI) in relation to clinical findings of TMD pain. Methods Thirty-six female patients with chronic rTMD or gTMD with at least 3 months duration were included in the study. Ten healthy women were included as controls. All participants completed a questionnaire that comprised assessment of degrees of depression, anxiety, stress, catastrophizing, pain intensity, disability and locations. A clinical Diagnostic Criteria for Temporomandibular Disorders examination that comprised assessment of pain locations, headache, mouth opening capacity, pain on mandibular movement, pain on palpation and temporomandibular joint noises was performed. Pressure-pain threshold (PPT) over the masseter muscle and temporal summation to pressure stimuli were assessed with an algometer. Within a week all participants underwent non-contrast enhanced MRI on a 3T MR scanner assessing T1-w and T2-w fluid attenuation inversion recovery. A single-voxel 1H-MRS examination using point-resolved spectroscopy was performed. The metabolite concentrations of NAA, tCr, Cho, MI, Glu and Glx were analyzed with the LC model. Metabolite levels were calculated as absolute concentrations, normalized to the water signal. Metabolite concentrations were used for statistical analysis from the LC model if the Cramér-Rao bounds were less than 20%. In addition, the ratios NAA/tCr, Cho/tCr, Glu/tCr and MI/tCr were calculated. Results The results showed significantly higher tCr levels within the posterior insula in patients with rTMD or gTMD pain than in HI (p=0.029). Cho was negatively correlated to maximum mouth opening capacity with or without pain (rs=-0.42, n=28, p=0.031 and rs=-0.48, n=28, p=0.034, respectively) as well as pressure-pain threshold on the hand (rs=-0.41, n=28, p=0.031). Glu was positively correlated to temporal summation to painful mechanical stimuli (rs=0.42, n=26, p=0.034). Conclusions The present study found that increased concentrations of Cho and Glu in the posterior insular cortex is related to clinical characteristics of chronic TMD pain, including generalized pain. These findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations. Implications The findings in this study have indirect implications for the diagnosis and management of TMD patients. That said, the findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations. It is also a further step towards understanding and accepting chronic pain as a disorder in itself.

Effects of Hospital-Based Physical Therapy on Hospital Discharge Outcomes among Hospitalized Older Adults with Community-Acquired Pneumonia and Declining Physical Function.

To examine whether hospital-based physical therapy is associated with functional changes and early hospital readmission among hospitalized older adults with community-acquired pneumonia and declining physical function. Study design was a retrospective observation study. Participants were community-dwelling older adults admitted to medicine floor for community-acquired pneumonia (n = 1,058). Their physical function using Katz activities of daily living (ADL) Index declined between hospital admission and 48 hours since hospital admission (Katz ADL Index 6→5). The intervention group was those receiving physical therapy for ≥ 0.5 hour/day. Outcomes were Katz ADL Index at hospital discharge and all-cause 30-day hospital readmission rate. The intervention and control groups did not differ in the Katz ADL Index at hospital discharge (p = 0.11). All-cause 30-day hospital readmission rate was lower in the intervention than in control groups (OR = 0.65, p = 0.02). Hospital-based physical therapy has the benefits toward reducing 30-day hospital readmission rate of acutely ill older adults with community-acquired pneumonia and declining physical function.

Associations between the 2007 Medicare reimbursement reduction for bone mineral density testing and osteoporosis drug therapy patterns of female Medicare beneficiaries.

OBJECTIVE: To examine how drug therapy patterns for osteoporosis have changed after the Medicare Physician Fee Schedule (MPFS) reimbursement reduction in 2007, in relation to follow-up bone mineral density (BMD) testing status. METHODS: We used a retrospective temporal shift design to examine changes in drug therapy patterns before (Phase 1: January 1, 2005-December 31, 2006) and after (Phase 2: July 1, 2007-June 30, 2009) the MPFS reimbursement reduction in 2007, Cleveland, OH, USA. Participants were osteoporotic older women in Phase 1 (n=1,340) and Phase 2 (n=1,437). The main outcomes were a) adherence, b) adjustment, c) occurrence of an extended gap, and d) restarting drug therapy after an extended gap. Follow-up BMD testing status by study phase and location were also analyzed. RESULTS: BMD testing rates at physicians' offices decreased from 64.5% in Phase 1 to 58.4% in Phase 2 (P=0.02); however, testing rates in hospital outpatient settings increased (from 20.8% to 24.5%). There were also decreases in drug therapy adjustment from 15.9% in Phase 1 to 11.6% in Phase 2 (odds ratio [OR]: 0.73; P<0.01) and in restarting drug therapy after an extended gap (55.4% in Phase 1 and 43.6% in Phase 2; OR: 0.76; P<0.01). CONCLUSION: There were no changes in the overall rate of follow-up BMD testing. The rates of drug adjustments and restarting drug therapy after an extended gap did decrease. These decreases were more evident when follow-up BMD testing was not performed.

The effects of shared situational awareness on functional and hospital outcomes of hospitalized older adults with heart failure.

BACKGROUND: Functional decline of hospitalized older adults is common and triggers health care expenditures. Physical therapy can retard the functional decline that occurs during hospitalization. This study aims to examine whether shared situational awareness (SSA) intervention may enhance the benefits of physical therapy for hospitalized older persons with a common diagnosis, heart failure. METHOD: An SSA intervention that involved daily multidisciplinary meetings was applied to the care of functionally declining older adults admitted to the medicine floor for heart failure. Covariates were matched between the intervention group (n=473) and control group (n=475). Both intervention and control groups received physical therapy for ≥0.5 hours per day. The following three outcomes were compared between groups: 1) disability, 2) transition to skilled nursing facility (SNF, post-acute care setting), and 3) 30-day readmission rate. RESULTS: Disability was lower in the intervention group (28%) than in the control group (37%) (relative risk [RR] =0.74; 95% confidence interval [CI], 0.35-0.97; P=0.026), and transition to SNF was lower in the intervention group (22%) than in the control group (30%) (RR =0.77; 95% CI, 0.39-0.98; P=0.032). The 30-day readmission rate did not significantly differ between the two groups. CONCLUSION: SSA intervention enhanced the benefits of physical therapy for functionally declining older adults. When applied to older adults with heart failure in the form of daily multidisciplinary meetings, SSA intervention improved functional outcomes and reduced transfer to SNFs after hospitalization.

Culturally Sensitive Depression Assessment for Chinese American Immigrants: Development of a Comprehensive Measure and a Screening Scale Using an Item Response Approach.

The present mixed methods study developed a comprehensive measure and a screening scale of depression for Chinese American immigrants by combining an emic approach with item response analysis. Clinical participants were immigrants diagnosed by licensed clinicians who worked in the community. Qualitative interviews with clinicians and clinical participants (N = 63) supported the definition of the construct of depression-which guided scale development-and a 47-item pilot scale. Clinical and community participants (N = 227) completed the pilot scale and measures of neurasthenia and acculturative stress, and the Patient Health Questionnaire Depression Module (PHQ-9). A Rasch Partial Credit Model of 42-items-representing psychological, somatic and interpersonal domains of distress-best fit the data. Twenty-three items overlapped with the DSM-IV symptoms of major depression. Twenty-seven items were biased by acculturation-related variables. Nine items appropriate for self-report screening in primary care and community organizations were chosen to form a brief scale. Both measures showed strong reliability and concurrent and convergent validity. The 9-item scale had better content validity than the PHQ-9. Implications regarding the impact of culture for assessment are highlighted.

Diosgenin modulates vascular smooth muscle cell function by regulating cell viability, migration, and calcium homeostasis.

In this study, we compared the potencies of diosgenin, a plant-derived sapogenin structurally similar to estrogen and progesterone, on vascular smooth muscle functions ranging from contraction and migration to apoptosis. The effects of diosgenin on vascular smooth muscle cell viability and migration were measured using a primary mouse aortic smooth muscle cell culture. The effects of diosgenin on smooth muscle cell contraction and calcium signaling were investigated in the isolated mouse aorta using wire myography and confocal microscopy, respectively. Here, we report that in cultured cells diosgenin (≥ 25 µM) induces apoptosis as measured by the number of annexin V-positive cells and caspase-3 cleavage, while decreasing cell viability as indicated by protein kinase B/Akt phosphorylation. In addition, diosgenin blocks smooth muscle cell migration in a transwell Boyden chamber in response to serum treatment and response to injury in a cell culture system. Diosgenin (≥ 25 µM) also significantly blocks receptor-mediated calcium signals and smooth muscle contraction in the isolated aorta. There is no difference in the inhibitory effects of diosgenin on vascular smooth muscle contraction between the endothelium-intact and endothelium-denuded aortic segments, indicating that they are caused by altered smooth muscle activity. Our findings suggest that over the concentration range of 10 to 15 µM diosgenin may provide overall beneficial effects on diseased vascular smooth muscle cells by blocking migration and contraction without any significant cytopathic effects, implying a potential therapeutic value for diosgenin in vascular disorders.

FcRgamma activation regulates inflammation-associated squamous carcinogenesis.

Chronically activated leukocytes recruited to premalignant tissues functionally contribute to cancer development; however, mechanisms underlying pro- versus anti-tumor programming of neoplastic tissues by immune cells remain obscure. Using the K14-HPV16 mouse model of squamous carcinogenesis, we report that B cells and humoral immunity foster cancer development by activating Fcgamma receptors (FcgammaRs) on resident and recruited myeloid cells. Stromal accumulation of autoantibodies in premalignant skin, through their interaction with activating FcgammaRs, regulate recruitment, composition, and bioeffector functions of leukocytes in neoplastic tissue, which in turn promote neoplastic progression and subsequent carcinoma development. These findings support a model in which B cells, humoral immunity, and activating FcgammaRs are required for establishing chronic inflammatory programs that promote de novo carcinogenesis.