Effects of evocalcet on parathyroid calcium-sensing receptor and vitamin D receptor expression in uremic rats.

Little is known about the effect of the recently developed calcimimetic evocalcet (Evo) on parathyroid calcium-sensing receptor (CaSR) and vitamin D receptor (VDR) expression. We examined the effects of Evo and cinacalcet (Cina) on CaSR and VDR expression in 5/6 nephrectomized Sprague-Dawley rats fed a high-phosphorus diet for 4 weeks to develop secondary hyperparathyroidism (SHPT). These uremic rats were divided into 4 groups-baseline control (Nx4W) and groups with additional treatment with either the Vehicle, Evo, or Cina for 2 weeks; normal rats were used as normal controls (NC). Blood parameters and parathyroid tissue were analyzed. CaSR and VDR expression levels were determined using immunohistochemistry. The degree of kidney injury and hyperphosphatemia was similar in the uremic groups (Nx4W, Vehicle, Cina, and Evo). Serum parathyroid hormone levels were significantly higher in the Nx4W and Vehicle groups than in the NC group. This increase was significantly suppressed in the Cina and Evo groups compared with that in the Vehicle group. Serum calcium levels were significantly and equally lower in the Cina and Evo groups relative to those in the Vehicle group. CaSR expression was significantly lower in the Nx4W and Vehicle groups than in the NC group. This downregulation was of an equally lesser magnitude in the Cina and Evo groups. A similar trend was observed for VDR expression. These results indicate that Evo and Cina treatment can increase parathyroid CaSR and VDR expression in uremic rats with SHPT, which could provide better control of mineral and bone disorder markers.

Fibroblast Growth Factor 23 Exacerbates Cardiac Fibrosis in Deoxycorticosterone Acetate-Salt Mice With Hypertension.

Fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease in patients with chronic kidney disease; however, the mechanisms underlying the effect of FGF23 on cardiac function remain to be investigated. Herein, we studied the effect of continuous intravenous (CIV) FGF23 loading in a deoxycorticosterone acetate (DOCA)-salt mouse model with mild chronic kidney disease and hypertension as well as heart failure with a preserved ejection fraction. Wild-type male mice were randomly allocated to 4 groups: normal control, vehicle-treated DOCA-salt mice, FGF23-treated DOCA-salt mice, and FGF23- and calcitriol-treated DOCA-salt mice. The DOCA-salt mice received the agents via the CIV route for 10 days using an infusion minipump. DOCA-salt mice that received FGF23 showed a marked increase in the serum FGF23 level, and echocardiography in these mice revealed heart failure with a preserved ejection fraction. These mice also showed exacerbation of myocardial fibrosis, concomitant with an inverse and significant correlation with Cyp27b1 expression. Calcitriol treatment attenuated FGF23-induced cardiac fibrosis and improved diastolic function via inhibition of transforming growth factor-ß signaling. This effect was independent of the systemic and local levels of FGF23. These results suggest that CIV FGF23 loading exacerbates cardiac fibrosis and that locally abnormal vitamin D metabolism is involved in this mechanism. Calcitriol attenuates this exacerbation by mediating transforming growth factor-ß signaling independently of the FGF23 levels.

One-Year Romosozumab Treatment Followed by One-Year Denosumab Treatment for Osteoporosis in Patients on Hemodialysis: An Observational Study.

There is limited evidence on the use of romosozumab (ROMO) in the treatment of osteoporosis in patients on hemodialysis (HD); thus, we aimed to investigate this topic. This prospective, observational, single-center cohort study included 13 prior osteoporosis treatment-naïve patients on HD with osteoporosis. They first received ROMO once monthly for 12 months (210 mg; subcutaneously once every month). Thereafter, they received denosumab (DENO) for an additional 12 months (60 mg; subcutaneously once every 6 months). We examined the incidence of new fractures; treatment safety; and temporal changes in the bone mineral density (BMD), bone metabolism markers, and vascular calcification. No new cases of fractures were noted. The median one-year percentage changes (from the baseline) in the BMDs at the lumbar spine (LS), total hip (TH), and femoral neck (FN) were + 9.0%, + 2.5%, and + 4.7%, respectively. These changes were maintained for 24 months. The corresponding relative changes from the baseline to 24 months thereafter were + 14.9%, + 5.4%, and + 6.5%, respectively. The percentage changes in TH BMD and FN BMD were negatively correlated with baseline BMD. Coronary artery and thoracic aorta calcification scores increased slightly from baseline to 12 months thereafter. However, fatal events (cardiovascular disease-associated and all-cause deaths) did not occur during ROMO treatment. Effectiveness of ROMO was better in patients who had severe osteoporosis with low TH BMD, low FN BMD, and high tartrate-resistant acid phosphatase 5b level at ROMO initiation.

Cdc42 has important roles in postnatal angiogenesis and vasculature formation.

Cdc42, a Rho family low molecular weight G protein, has important roles in various cell functions, including cytoskeletal rearrangement, cell adhesion and cell proliferation and differentiation. To investigate the involvement of Cdc42 in the activities of vascular endothelial cells, we generated Cdc42 conditional knockout mice in which Cdc42 was time -specifically deficient in vascular endothelial cells (Cdc42 â€‹fl/fl; VE-Cad CreERT: Cdc42 cKO). When the Cdc42 gene was deleted after birth, Cdc42 cKO mice were smaller than the control mice, and died between postnatal day 8 (P8) and P10. Necropsy findings confirmed that these mice had various pathological aberrances in the vessels of most organs, such as blood flow congestion and blood cell invasion. Electron microscopic observations also revealed that capillary endothelial cells were detached from the basement membrane as well as phagocytosis of dead endothelial cells induced by macrophages. Moreover, vascular sprouting from aortic rings induced by VEGF-A was diminished in samples from the Cdc42 cKO mice because of an endothelial cell proliferation defect. These results suggest that Cdc42 in vascular endothelial cells has important roles in blood vessel formation after birth.

An individualized treatment rule to optimize probability of remission by continuation, switching, or combining antidepressant medications after failing a first-line antidepressant in a two-stage randomized trial.

BACKGROUND: There is growing interest in using composite individualized treatment rules (ITRs) to guide depression treatment selection, but best approaches for doing this are not widely known. We develop an ITR for depression remission based on secondary analysis of a recently published trial for second-line antidepression medication selection using a cutting-edge ensemble machine learning method. METHODS: Data come from the SUN(^_^)D trial, an open-label, assessor blinded pragmatic trial of previously-untreated patients with major depressive disorder from 48 clinics in Japan. Initial clinic-level randomization assigned patients to 50 or 100 mg/day sertraline. We focus on the 1549 patients who failed to remit within 3 weeks and were then rerandomized at the individual-level to continuation with sertraline, switching to mirtazapine, or combining mirtazapine with sertraline. The outcome was remission 9 weeks post-baseline. Predictors included socio-demographics, clinical characteristics, baseline symptoms, changes in symptoms between baseline and week 3, and week 3 side effects. RESULTS: Optimized treatment was associated with significantly increased cross-validated week 9 remission rates in both samples [5.3% (2.4%), p = 0.016 50 mg/day sample; 5.1% (2.7%), p = 0.031 100 mg/day sample] compared to randomization (30.1-30.8%). Optimization was also associated with significantly increased remission in both samples compared to continuation [24.7% in both: 11.2% (3.8%), p = 0.002 50 mg/day sample; 11.7% (3.9%), p = 0.001 100 mg/day sample]. Non-significant gains were found for optimization compared to switching or combining. CONCLUSIONS: An ITR can be developed to improve second-line antidepressant selection, but replication in a larger study with more comprehensive baseline predictors might produce stronger and more stable results.

Osteoblastic differentiation of bone marrow mesenchymal stem cells in uremic rats.

Severe secondary hyperparathyroidism (SHPT) represents a high turnover bone disease, osteitis fibrosa, but the pathogenesis of osteitis fibrosa remains to be fully elucidated. We examined the characteristics of the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts in uremic rats. We bred 5/6 nephrectomized (Nx) rats with a high phosphorus (P) diet to induce SHPT (Nx + HP), or Nx (Nx + ND) and normal rats (Nc + ND) fed a standard diet (ND). After 8 weeks, BMSCs were isolated from the femur and serum were analyzed. BMSCs underwent flow cytometric examination for the expression patterns of cell surface markers (CD90+, CD29+, CD45-, and CD31-). Serum creatinine (Cre) levels were significantly elevated in the Nx + NP rats compared with the Nc + NP rats. Cre levels in the Nx + HP rats were levels to those in the Nx + ND rats. Serum P and PTH levels were significantly elevated in the Nx + HP rats compared with the Nx + ND rats. Bone morphometrical analysis showed increases in both osteoid volume and eroded surfaces in the Nx + HP but not in the Nx + ND rats. The populations of harvested BMSCs were similar between all three groups. Alp, Runx2, Pth1r and Cyclin D1 mRNA expression in the BMSCs from the Nx + ND rats were significantly suppressed compared with those isolated from the Nc + ND groups. Alizarin red staining tended to be similar to the expression of these mRNA. These results suggest that the BMSCs differentiation into osteoblasts was disturbed in the uremic rats.

Cdc42 regulates cranial suture morphogenesis and ossification.

Cdc42 (cell division cycle 42) is ubiquitously expressed small GTPases belonging to the Rho family of proteins. Previously, we generated limb bud mesenchyme-specific Cdc42 inactivated mice (Cdc42 conditional knockout mice; Cdc42 fl/fl; Prx1-Cre), which showed short limbs and cranial bone deformities, though the mechanism related to the cranium phenotype was unclear. In the present study, we investigated the role of Cdc42 in cranial bone development. Our results showed that loss of Cdc42 caused a defect of intramembranous ossification in cranial bone tissues which is related to decreased expressions of cranial suture morphogenesis genes, including Indian hedgehog (Ihh) and bone morphogenetic proteins (BMPs). These findings demonstrate that Cdc42 plays a crucial role in cranial osteogenesis, and is controlled by Ihh- and BMP-mediated signaling during cranium development.

Nephronectin Expression is Inhibited by Inorganic Phosphate in Osteoblasts.

Nephronectin (Npnt), an extracellular matrix protein, is known to be a ligand of integrin α8ß1, and it has also been known to play critical roles as various organs. In the present study, elevated extracellular inorganic phosphate (Pi) strongly inhibited the expression of Npnt in MC3T3-E1 cells, while the existence of extracellular calcium (Ca) was indispensable for its effect. Furthermore, Pi-induced inhibition of Npnt gene expression was recovered by inhibitors of both sodium-dependent Pi transporter (Pit) and fibroblast growth factor receptors (Fgfrs). These results demonstrated that Npnt gene expression is regulated by extracellular Pi via Pit and Fgfrs.

Prediction of remission in pharmacotherapy of untreated major depression: development and validation of multivariable prediction models.

BACKGROUND: Depression is increasingly recognized as a chronic and relapsing disorder. However, an important minority of patients who start treatment for their major depressive episode recover to euthymia. It is clinically important to be able to predict such individuals. METHODS: The study is a secondary analysis of a recently completed pragmatic megatrial examining first- and second-line treatments for hitherto untreated episodes of non-psychotic unipolar major depression (n = 2011). Using the first half of the cohort as the derivation set, we applied multiply-imputed stepwise logistic regression with backward selection to build a prediction model to predict remission, defined as scoring 4 or less on the Patient Health Quetionnaire-9 at week 9. We used three successively richer sets of predictors at baseline only, up to week 1, and up to week 3. We examined the external validity of the derived prediction models with the second half of the cohort. RESULTS: In total, 37.0% (95% confidence interval 34.8-39.1%) were in remission at week 9. Only the models using data up to week 1 or 3 showed reasonable performance. Age, education, length of episode and depression severity remained in the multivariable prediction models. In the validation set, the discrimination of the prediction model was satisfactory with the area under the curve of 0.73 (0.70-0.77) and 0.82 (0.79-0.85), while the calibration was excellent with non-significant goodness-of-fit χ2 values (p = 0.41 and p = 0.29), respectively. CONCLUSIONS: Patients and clinicians can use these prediction models to estimate their predicted probability of achieving remission after acute antidepressant therapy.

Cooperation of Rho family proteins Rac1 and Cdc42 in cartilage development and calcified tissue formation.

Rac1 and Cdc42, Rho family low molecular weight G proteins, are intracellular signaling factors that transmit various information from outside to inside cells. Primarily, they are known to control various biological activities mediated by actin cytoskeleton reorganization, such as cell proliferation, differentiation, and apoptosis. In order to investigate the functions of Rac1 and Cdc42 in bone formation, we prepared cartilage-specific double conditional knockout mice, Rac1fl/fl; Cdc42fl/fl; Col2-Cre (Rac1: Cdc42 dcKO mice), which died just after birth, similar to Cdc42fl/fl; Col2-Cre mice (Cdc42 cKO mice). Our findings showed that the long tubule bone in Rac1: Cdc42 dcKO mice was shorter than that in Rac1fl/fl; Col2-Cre mice (Rac1 cKO mice) and Cdc42 cKO mice. Abnormal skeleton formation was also observed and disordered columnar formation in the growth plate of the Rac1: Cdc42 dcKO mice was more severe as compared to the Rac1 cKO and Cdc42 cKO mice. Together, these results suggest that Rac1 and Cdc42 have cooperating roles in regulation of bone development.

Optimising first- and second-line treatment strategies for untreated major depressive disorder - the SUN☺D study: a pragmatic, multi-centre, assessor-blinded randomised controlled trial.

BACKGROUND: For patients starting treatment for depression, current guidelines recommend titrating the antidepressant dosage to the maximum of the licenced range if tolerated. When patients do not achieve remission within several weeks, recommendations include adding or switching to another antidepressant. However, the relative merits of these guideline strategies remain unestablished. METHODS: This multi-centre, open-label, assessor-blinded, pragmatic trial involved two steps. Step 1 used open-cluster randomisation, allocating clinics into those titrating sertraline up to 50 mg/day or 100 mg/day by week 3. Step 2 used central randomisation to allocate patients who did not remit after 3 weeks of treatment to continue sertraline, to add mirtazapine or to switch to mirtazapine. The primary outcome was depression severity measured with the Patient Health Questionnaire-9 (PHQ-9) (scores between 0 and 27; higher scores, greater depression) at week 9. We applied mixed-model repeated-measures analysis adjusted for key baseline covariates. RESULTS: Between December 2010 and March 2015, we recruited 2011 participants with hitherto untreated major depression at 48 clinics in Japan. In step 1, 970 participants were allocated to the 50 mg/day and 1041 to the 100 mg/day arms; 1927 (95.8%) provided primary outcomes. There was no statistically significant difference in the adjusted PHQ-9 score at week 9 between the 50 mg/day arm and the 100 mg/day arm (0.25 point, 95% confidence interval (CI), - 0.58 to 1.07, P = 0.55). Other outcomes proved similar in the two groups. In step 2, 1646 participants not remitted by week 3 were randomised to continue sertraline (n = 551), to add mirtazapine (n = 537) or to switch to mirtazapine (n = 558): 1613 (98.0%) provided primary outcomes. At week 9, adding mirtazapine achieved a reduction in PHQ-9 scores of 0.99 point (0.43 to 1.55, P = 0.0012); switching achieved a reduction of 1.01 points (0.46 to 1.56, P = 0.0012), both relative to continuing sertraline. Combination increased the percentage of remission by 12.4% (6.1 to 19.0%) and switching by 8.4% (2.5 to 14.8%). There were no differences in adverse effects. CONCLUSIONS: In patients with new onset depression, we found no advantage of titrating sertraline to 100 mg vs 50 mg. Patients unremitted by week 3 gained a small benefit in reduction of depressive symptoms at week 9 by switching sertraline to mirtazapine or by adding mirtazapine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01109693 . Registered on 23 April 2010.

Brief multifamily Psychoeducation for family members of patients with chronic major depression: a randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is a common and often chronic problem. Patients with chronic MDD often have negative impacts on the health of their families. Family psychoeducation is recognized as part of the optimal treatment for patients with psychotic disorder, and has been shown to reduce the rate of relapse in individuals with schizophrenia and to reduce the burden on their caregivers. Thus, we predict that family psychoeducation has the potential to reduce the burden on the caregivers of patients with chronic MDD. In the present study, we aimed to investigate the effects of brief multifamily psychoeducation (BMP) on the mental health status of family members of patients with chronic MDD. METHODS: We conducted a clinical trial consisting of 49 chronic MDD patients and their families. Each family was randomly assigned to either the BMP intervention group or the control group. The intervention group received four BMP sessions, once every two weeks for eight weeks. The control group received one counseling session administered by a nurse. All patients received standard treatment administered by physicians. The primary outcome measurement was the Kessler Screening Scale for Psychological Distress (K6) score of family members at 16- weeks after the first BMP session. Secondary outcomes were depressive symptoms of both family members and patients at multiple time points, as well as family functioning as evaluated by the patients. Intention-to-treat analyses were conducted. RESULTS: There was no statistically significant effect of BMP on K6 scores at 16- weeks (mean difference 1.17, 95% confidence interval: - 0.63 to 2.98, P = 0.19). Exploratory analyses revealed that BMP reduced depressive symptoms in family members at 8- weeks (difference = - 3.37, 95%CI -6.32 to - 0.43, P = 0.02) and improved family functioning at multiple time points (Role; 8 W, difference = - 0.13, 95%CI -0.26 to - 0.00, P = 0.04, Affective Responsiveness; 8 W, difference = - 0.24, 95%CI -0.43 to - 0.05, P = 0.01, 32 W, difference = - 0.22, 95%CI -0.41 to - 0.03, P = 0.02, Behavior Control; 16 W, difference = - 0.17, 95%CI -0.34 to - 0.00, P = 0.04). CONCLUSIONS: Four BMP sessions did not significantly reduce the psychological distress of family members of patients with chronic MDD. TRIAL REGISTRATION: Clinical Trials. gov NCT01734291 , retrospectively registered (Registration date: November 21, 2012).

Correction: Smartphone Cognitive Behavioral Therapy as an Adjunct to Pharmacotherapy for Refractory Depression: Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/jmir.8602.].

IL-1ß suppresses nephronectin expression in osteoblasts via ERK1/2 and JNK.

Nephronectin (Npnt), an extracellular matrix protein, is considered to play critical roles in development of various tissues and their functions. In basic science experiments, we found that interleukin-1ß (IL-1ß), well known to have an important role in inflammatory response, inhibited Npnt gene expression in MC3T3-E1 cells, a mouse osteoblastic cell line. The purpose of this study was to investigate mechanisms that govern the regulation of Npnt gene expression by IL-1ß in osteoblasts.

Smartphone Cognitive Behavioral Therapy as an Adjunct to Pharmacotherapy for Refractory Depression: Randomized Controlled Trial.

BACKGROUND: In the treatment of major depression, antidepressants are effective but not curative. Cognitive behavioral therapy (CBT) is also effective, alone or in combination with pharmacotherapy, but accessibility is a problem. OBJECTIVE: The aim is to evaluate the effectiveness of a smartphone CBT app as adjunctive therapy among patients with antidepressant-resistant major depression. METHODS: A multisite, assessor-masked, parallel-group randomized controlled trial was conducted in 20 psychiatric clinics and hospitals in Japan. Participants were eligible if they had a primary diagnosis of major depression and were antidepressant-refractory after taking one or more antidepressants at an adequate dosage for four or more weeks. After a 1-week run-in in which participants started the medication switch and had access to the welcome session of the app, patients were randomized to medication switch alone or to medication switch plus smartphone CBT app via the centralized Web system. The smartphone app, called Kokoro-app ("kokoro" means "mind" in Japanese), included sessions on self-monitoring, behavioral activation, and cognitive restructuring presented by cartoon characters. The primary outcome was depression severity as assessed by masked telephone assessors with the Patient Health Questionnaire-9 (PHQ-9) at week 9. The secondary outcomes included the Beck Depression Inventory-II (BDI-II) and Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER). RESULTS: In the total sample (N=164), 81 participants were allocated to the smartphone CBT in addition to medication change and 83 to medication change alone. In the former group, all but one participant (80/81, 99%) completed at least half, and 71 (88%) completed at least six of eight sessions. In the intention-to-treat analysis, patients allocated the CBT app scored 2.48 points (95% CI 1.23-3.72, P<.001; standardized mean difference 0.40) lower on PHQ-9 than the control at week 9. The former group also scored 4.1 points (95% CI 1.5-6.6, P=.002) lower on BDI-II and 0.76 points (95% CI -0.05 to 1.58, P=.07) lower on FIBSER. In the per-protocol sample (comfortable with the smartphone app, still symptomatic, and adherent to medication with mild or less side effects after run-in), the intervention group (n=60) scored 1.72 points (95% CI 0.25-3.18, P=.02) lower on PHQ-9, 3.2 points (95% CI -0.01 to 6.3, P=.05) lower on BDI-II, and 0.75 points (95% CI 0.03-1.47, P=.04) lower on FIBSER than the control (n=57). The treatment benefits were maintained up to week 17. CONCLUSIONS: This is the first study to demonstrate the effectiveness of a smartphone CBT in the treatment of clinically diagnosed depression. Given the merits of the mobile mental health intervention, including accessibility, affordability, quality control, and effectiveness, it is clinically worthwhile to consider adjunctive use of a smartphone CBT app when treating patients with antidepressant-resistant depression. Research into its effectiveness in wider clinical contexts is warranted. TRIAL REGISTRATION: Japanese Clinical Trials Registry UMIN CTR 000013693; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R000015984 (Archived by WebCite at http://www.webcitation.org/6u6pxVwik).

Effects of Oscillatory Shear on the Orientation of the Inverse Bicontinuous Cubic Phase in a Nonionic Surfactant/Water System.

The bicontinuous inverse cubic phase (V2 phase) formed in amphiphilic systems consists of bilayer networks with a long-range order. We have investigated effects of oscillatory shear on the orientation of the V2 phase with space group Ia3d formed in a nonionic surfactant (C12E2)/water system by using simultaneous measurements of rheology/small-angle X-ray scattering. It is shown that grain refining occurs by applying the large amplitude oscillatory shear (LAOS) with a strain amplitude (γ0) of ∼20, which gives the ratio of the loss modulus (G″) to the storage modulus (G') (G″/G' = tan δ) of ∼100. On the other hand, orientation of the cubic lattice occurs when the small amplitude (γ0 ≈ 0.0004) oscillatory shear (SAOS) in the linear regime is applied to the sample just after the LAOS. Interestingly, the orientation is strongly enhanced by the "medium amplitude" (γ0 ≈ 0.05) oscillatory shear ("MAOS") after the SAOS. When the MAOS is applied before applying the LAOS, orientation to a particular direction is not observed, indicating that the grain refining process by the LAOS is necessary for the orientation during the MAOS. The results of additional experiments show that the shear sequence "LAOS-MAOS" is effective for the orientation of the cubic lattice. When the LAOS and MAOS are applied to the sample alternatively, grain refining and orientation occur during the LAOS and MAOS, respectively, indicating reversibility of the orientation. It is shown that (i) the degree of the orientation is dependent on γ0 and the frequency (ω) of the MAOS and (ii) relatively higher orientation can be obtained for the combination of γ0 and ω, which gives tan δ = 2-3. The lattice constant does not change throughout all the shearing processes and is equal to that before shearing within the experimental errors, indicating that the shear melting does not occur. These results suggest a possibility to control the orientation of the cubic lattice only by changing the conditions of oscillatory shear without using the epitaxial transition from other anisotropic phases, such as the hexagonal and lamellar phases.

Rapid diagnostic method for the identification of Mycoplasma pneumoniae respiratory tract infection.

Rapid diagnostic tests are useful tools in the early diagnosis of respiratory tract infections (RTIs) caused by a specific pathogens. We investigated the sensitivity and specificity of a rapid and simple antigen test for the detection of Mycoplasma pneumoniae, Ribotest Mycoplasma(®) in adolescent and adult patients with RTIs. In addition, we evaluated the accuracy of clinical and laboratory findings for the early presumptive diagnosis of M. pneumoniae RTI. We compared 55 cases with laboratory-confirmed M. pneumoniae infection using serology, culture, and polymerase chain reaction (PCR) and 346 cases without laboratory-confirmed M. pneumoniae infection. Pneumonia cases were excluded in this study. Among patients with M. pneumoniae infection, the incidences of cough, sore throat, and sputum production were high, with rates of 98%, 61%, and 67%, respectively, but the specificity was low. The prevalence of nasal symptoms was significantly lower in patients with M. pneumoniae infection (9%) than in non-M. pneumoniae infection (70%; p < 0.0001). When PCR was used as the control test, the sensitivity, specificity, and overall agreement rates with Ribotest(®) were 71%, 89%, and 87%, respectively. Clinical symptoms and laboratory data were of limited value in making the diagnosis of M. pneumoniae RTI in adolescent and adult patients. Our results suggested that Ribotest(®) may be helpful in distinguishing M. pneumoniae RTI patients from those without the disease. Physicians should consider the use of Ribotest(®) when patients have a persistent cough without nasal symptoms.

Changes in physical function after hospitalization in patients with nursing and healthcare-associated pneumonia.

To clarify the functional changes after hospitalization due to pneumonia in elderly Japanese patients, we investigated the changes in physical functioning, nutritional routes, and diet that occurred after hospitalization in patients with nursing and healthcare-associated pneumonia (NHCAP). We analyzed 405 patients with NHCAP and compared findings with 448 patients with community-acquired pneumonia (CAP). Among the NHCAP patients, 140 (34%) patients showed a decline in activities of daily living function between baseline and discharge. After hospital discharge, 149 (37%) NHCAP patients did not return to the same residence location compared with where they were living prior to hospital admission. The frequency of this outcome was significantly higher in NHCAP patients than in CAP patients (p < 0.0001). After 6 months' follow-up, of the patients who transferred to different hospitals, 41 (73%) patients with CAP had returned to their own home, but only 16 (20%) patients with NHCAP could return home (p < 0.0001). Rates of alteration of nutritional route and type of diet from oral nutrition were significantly higher in NHCAP patients compared with CAP patients (22% vs 4%, p < 0.0001). Our results demonstrated that approximately one-third of hospitalized patients with NHCAP showed a decline in physical function. In addition, approximately one-fifth of NHCAP patients had changed their route of nutrition and type of diet. Our results indicated that physicians should attach greater importance to preventative measures against NHCAP rather than relying on antibiotic therapy post-infection in the management of pneumonia in elderly patients in order to extend their healthy life expectancy.