Coronavirus disease 2019 (COVID-19) has been spreading globally since 2019；however, comprehensive rehabilitation of elderly patients with COVID-19 pneumonia remains a challenge. A 76-year-old American woman with COVID-19 pneumonia was admitted to our hospital. Because her disease was complicated by acute respiratory distress syndrome (ARDS), she was treated with intensive care, including invasive ventilation and extracorporeal membrane oxygenation (ECMO). During and after intensive care, she exhibited physical symptoms such as weakness, pain, shortness of breath, and difficulty in movement and exercise. Furthermore, during approximately 3.5 months of hospitalization, she received swallowing and speech therapies along with physical therapy. These rehabilitation therapies enabled her to get home in the United States. Her rehabilitation schedule had to be carefully planned according to her symptoms and infectiousness of COVID-19. This paper highlights few important points regarding the difficulty in rehabilitation including that of physical function, mental health, and cognitive function of patients with COVID-19. Furthermore, this report provides a problem-solving approach for long-term rehabilitation in elderly patients with COVID-19 pneumonia.

OBJECTIVES: We examined whether eldecalcitol (ELD) provided additive bone mineral density (BMD) and bone turnover marker gains in patients undergoing long-term bisphosphonate (BP) usage, especially in osteoporotic individuals exhibiting a poor response to BPs. METHODS: Forty-two post-menopausal patients with primary osteoporosis and low lumbar BMD (L-BMD) and/or bilateral total hip BMD (H-BMD) values receiving long-term BP treatment were prospectively enrolled. Serum bone alkaline phosphatase (BAP) was measured as a bone formation marker and urinary N-terminal telopeptide of type I collagen (NTX) was assessed as a bone resorption marker. L-BMD, H-BMD, and femoral neck BMD (N-BMD) were recorded before, at the commencement of, and during ELD administration. RESULTS: BAP and urinary NTX were significantly decreased by BP therapy prior to ELD. ELD addition further significantly decreased the bone turnover markers (both p < 0.01). The mean L-BMD increase rate was 0.2% (p = 0.81) from 2 to 1 years before ELD administration, −0.7% (p = 0.30) during the year before ELD, and 2.9% (p < 0.01) during 1 year of ELD. Similar findings were observed for the mean increase rate of H-BMD, with values of 0.2% (p = 0.55), −0.7% (p < 0.01), and 1.2% (p < 0.01), respectively. The mean N-BMD increase rate was significantly increased after ELD administration (1.1%, p = 0.03) despite no gains by BP therapy alone. CONCLUSIONS: This study suggests that ELD addition may be useful for osteoporotic patients exhibiting a diminished long-term BP therapy response.
Alkaline Phosphatase ; Bone Density ; Bone Remodeling ; Bone Resorption ; Collagen Type I ; Femur Neck ; Hip ; Humans ; Osteogenesis ; Osteoporosis ; Prospective Studies

OBJECTIVES: Increasing bone mineral density (BMD) to reduce fracture risk is a primary goal of osteoporosis treatment. This prospective, observational study evaluates the effects of monthly minodronate (MIN; 50 mg) with or without eldecalcitol (ELD) addition in osteoporosis patients with rheumatoid arthritis (RA) during 18 months. METHODS: The cohort was prospectively and randomly split into the MIN monotherapy group (14 cases) and MIN plus ELD group (combination group; 14 cases) due to no reports on the effectiveness and safety of MIN therapy in relation to ELD addition for comparisons of serum tartrate-resistant acid phosphatase (TRACP)-5b, bone alkaline phosphatase (BAP), and BMD of the lumbar 1–4 vertebrae (L-BMD), bilateral total hips (H-BMD; the mean value of the right and left hips), and bilateral femoral necks (FN-BMD) at baseline and at 6, 12, and 18 months of treatment. RESULTS: Baseline values were comparable between the groups apart from a tendency for higher TRACP5b in the combination group. Seven of 14 patients in the combination group had received previous bisphosphonate treatment. BAP was significantly more reduced in the monotherapy group at 6 months, with no other remarkable differences for TRACP5b, L-BMD, H-BMD, or FN-BMD during the observation period. CONCLUSIONS The above findings suggest that regardless of ELD addition, MIN potentially improves BMD during 18 months in osteoporosis patients with RA.

OBJECTIVES: The aim of this study was to examine the efficacy, safety, and adherence of ibandronate (IBN) treatment with or without vitamin D supplementation for 3 years in Japanese women with postmenopausal osteoporosis. METHODS: This prospective investigation included 27 patients treated with IBN alone (monotherapy group) and 29 patients receiving IBN and alfacalcidol (ALF) (combination group). Bone metabolism and bone mineral density (BMD) were measured before and at 18, 24, 30, and 36 months of therapy. Treatment discontinuation and fracture occurrence were assessed as well. RESULTS: Lumbar 1–4 BMD (L-BMD) was significantly increased in the monotherapy and combination groups by 3.9% and 7.2%, respectively, at 36 months, with significant gains in total hip BMD (H-BMD) of 3.7% and 4.9%, respectively. There were significant differences in L-BMD improvement between the groups at 18, 24, and 30 months (P < 0.05) and at 36 months (P < 0.01). Compared with pretreatment levels, the percentage changes of L-BMD and H-BMD were significant at all time points in the combination group and at all points apart from L-BMD at 36 months in the monotherapy group. In the monotherapy group, 14 patients dropped out during 3 years and 2 vertebral fractures occurred during the first year. In the combination group, 16 cases dropped out during 3 years and 1 nonvertebral fracture was noted during the first year. CONCLUSIONS: Our findings suggest that combination therapy of IBN and vitamin D is superior to monotherapy with regard to L-BMD improvements for 3 years, with both groups showing comparable safety and adherence to treatment.
Asian Continental Ancestry Group ; Bone Density ; Compliance ; Female ; Hip ; Humans ; Metabolism ; Osteoporosis ; Osteoporosis, Postmenopausal ; Prospective Studies ; Vitamin D

OBJECTIVES: This is an open labeled and retrospective cohort study which compared the effectiveness and safety of ibandronate (IBN) and minodronate (MIN) combined with eldecalcitol (ELD) in primary osteoporosis of women. METHODS: One hundred and forty-eight primary osteoporotic women were classified into 3 groups; 1) intravenous IBN combined with oral ELD (IBN + ELD group, N = 50; 81.8 ± 6.2 years), 2) oral MIN combined with oral ELD (MIN + ELD group, N = 50; 77.2 ± 6.9 years) and 3) oral ELD alone (ELD group, N = 48; 75.0 ± 8.3 years). For statistical analysis, L-BMD, H-BMD, serum corrected Ca, serum iP, intact-PTH, TRACP-5b, BAP, serum Hcy, eGFR and urine Ca/Cr ratio were measured until 12 months after the start of therapy. RESULTS: L-BMD values increased significantly in both IBN + ELD and MIN + ELD group, however, H-BMD increased significantly in the IBN + ELD group only. TRACP-5b values decreased rapidly during the first 6 months in both IBN + ELD and MIN + ELD group. However, BAP value in the IBN + ELD group decreased more gradually compared with that in the MIN + ELD group. Both serum Ca value and urine Ca/Cr ratio tended to increase, and the eGFR value decreased significantly in each group. CONCLUSIONS: IBN combined with ELD administration can act more effectively to increase BMD compared with MIN combined with ELD administration. Differences of decreasing rate in TRACP-5b and BAP value may lead to differences of increased rate of BMD in the IBN + ELD and MIN + ELD group. Because many cases of osteoporosis are elderly persons associated with chronic kidney disease, monitoring of kidney function and concentration of Ca in blood and urine is essential.
Aged ; Cohort Studies ; Female ; Follow-Up Studies* ; Humans ; Kidney ; Osteoporosis* ; Renal Insufficiency, Chronic ; Retrospective Studies

The electrogenic sodium/bicarbonate cotransporter 1 (NBCe1) on the basolateral side of the renal proximal tubule plays a pivotal role in systemic acid-base homeostasis. Mutations in the gene encoding NBCe1 cause severe proximal renal tubular acidosis accompanied by other extrarenal symptoms. The proximal tubule reabsorbs most of the sodium filtered in the glomerulus, contributing to the regulation of plasma volume and blood pressure. NBCe1 and other sodium transporters in the proximal tubule are regulated by hormones, such as angiotensin II and insulin. Angiotensin II is probably the most important stimulator of sodium reabsorption. Proximal tubule AT(1A) receptor is crucial for the systemic pressor effect of angiotensin II. In rodents and rabbits, the effect on proximal tubule NBCe1 is biphasic; at low concentration, angiotensin II stimulates NBCe1 via PKC/cAMP/ERK, whereas at high concentration, it inhibits NBCe1 via NO/cGMP/cGKII. In contrast, in human proximal tubule, angiotensin II has a dose-dependent monophasic stimulatory effect via NO/cGMP/ERK. Insulin stimulates the proximal tubule sodium transport, which is IRS2-dependent. We found that in insulin resistance and overt diabetic nephropathy, stimulatory effect of insulin on proximal tubule transport was preserved. Our results suggest that the preserved stimulation of the proximal tubule enhances sodium reabsorption, contributing to the pathogenesis of hypertension with metabolic syndrome. We describe recent findings regarding the role of proximal tubule transport in the regulation of blood pressure, focusing on the effects of angiotensin II and insulin.
Acidosis, Renal Tubular ; Angiotensin II ; Blood Pressure* ; Diabetic Nephropathies ; Homeostasis ; Humans ; Hypertension ; Insulin ; Insulin Resistance ; Kidney Tubules, Proximal ; Plasma Volume ; Rabbits ; Rodentia ; Sodium ; Sodium-Bicarbonate Symporters

OBJECTIVES: The aim of this study was to examine the discontinuation and occurrence of fracture during denosumab treatment in Japanese women with primary osteoporosis or rheumatoid arthritis (RA) with osteoporosis. METHODS: This retrospective study included 143 patients with primary osteoporosis and 96 patients with RA and osteoporosis who were treated with denosumab. Treatment discontinuation, fracture occurrence, lumbar spine (L1–4) bone mineral density (LS-BMD), and bilateral total hip BMD (TH-BMD) were examined before and at 1 and 2 years after treatment commencement. RESULTS: In the primary osteoporosis group, 32 cases dropped out and no fractures occurred from 0 to 1 year. Eighteen cases were lost to follow-up and no fractures were noted from 1 to 2 years. In the RA with osteoporosis group, 7 cases dropped out and no fracture occurred from 0 to 1 year. Twenty-one cases were lost to follow-up and 2 nonvertebral fractures were noted from 1 to 2 years. In this group, 13 cases dropped out from 1 to 2 years and 16 cases dropped out during the 2-year study period due to economic reasons. LS-BMD and TH-BMD values increased continuously for 2 years of treatment in both primary osteoporosis and RA with osteoporosis groups. CONCLUSIONS: These results suggest that during denosumab therapy, the discontinuation rate is expected to remain low during 2 years of treatment in primary osteoporotic patients. In RA patients with osteoporosis, however, the discontinuation rate may increase due to economic reasons from 1 to 2 years of therapy.
Arthritis, Rheumatoid* ; Asian Continental Ancestry Group* ; Bone Density ; Compliance* ; Denosumab* ; Female ; Hip ; Humans ; Lost to Follow-Up ; Osteoporosis* ; Retrospective Studies ; Spine

Objectives : A pharmacotherapeutic system for safe and proper use of warfarin was developed through physician-pharmacist cooperative practice ; its effects on patient adherence to therapeutic regimens and the therapeutic benefit of warfarin were assessed.
Methods : Subjects were 12 outpatients or home-care patients receiving warfarin. Patients' level of understanding of warfarin therapy and time in therapeutic range (TTR) were used as indices of adherence and therapeutic benefit, respectively. Before the physician examination, patients were interviewed by pharmacists using point-of-care testing with the CoaguChek ^®XS to check their prothrombin time-international normalized ratio (PT-INR). Pharmacists reported status of warfarin administration, any adverse effects, and medication management status to each patient's physician using the medication record or inter-institute information exchange sheet. Patient adherence was assessed before and after the pre-examination interview and changes in TTR were evaluated.
Results : Levels of understanding of warfarin therapy were significantly higher after pharmacists provided medication counseling (immediately before 4.8±1.9 vs 24 weeks after 6.8±2.4 ; P=0.0079, Wilcoxon signed-rank test). TTR significantly improved at 24 weeks after the interview (pre-interview 20.9±29.8% vs post-interview 60.5±30.5%, respectively ; P=0.0024, Wilcoxon signed-rank test).
Conclusion : The results suggest that patients'adherence to warfarin regimens and the therapeutic benefit of warfarin is improved by pharmacists'obtaining information on PT-INR before patients'medical examinations, as well as by utilizing this information to establish a cooperative pharmacotherapeutic system for good TTR management, as supported by a common protocol across pharmacies and medical institutions.

As a bisphosphonate, minodronate (MIN) is one of the strongest inhibitors of bone resorption. However, there have been no reports directly comparing the antiresorptive effects of monthly MIN with those of monthly risedronate (RIS). We enrolled 30 cases of osteoporosis (OP; 16 in the MIN group [mean age: 68.2 years] and 14 in the RIS group [mean age: 68.1 years]) to investigate the early effects of treatment by monthly MIN or RIS over a 4-month period using bone turnover marker values. Only female patients were enrolled to avoid gender bias. Urinary cross-linked N-telopeptide of type I collagen (NTX) before treatment and at 1, 2, and 4 months of therapy, as well as serum bone alkaline phosphatase and alkaline phosphatase before treatment and at 4 months afterwards, were evaluated. All bone turnover marker values were significantly decreased at 4 months in both groups. The changes in urinary NTX at the study end point for RIS and MIN were -30.1% and -63.1%, respectively. From 2 months of treatment, the antiresorptive effects on urinary NTX by MIN were significantly higher than those by RIS, indicating that MIN more immediately and strongly inhibited bone absorption. Thus, monthly MIN seems to suppress bone resorption faster and more strongly than RIS in OP treatment.
Absorption ; Alkaline Phosphatase ; Bone Remodeling ; Bone Resorption* ; Collagen Type I ; Female ; Humans ; Osteoporosis ; Risedronate Sodium* ; Sexism

Subclavian artery aneurysm (SCAA), a peripheral arterial aneurysm, is a rare entity. The surgical procedure and approach depend on the location of the aneurysm. We present a case of the endovascular therapy combined with cross axillary bypass. The patient was a 75-year-old man with a small abdominal aortic aneurysm. Multi-detector computed tomography (MDCT) revealed an intrathoracic right SCAA 38 mm in diameter. The operation was performed successfully under general anesthesia. After cross bypass of bilateral axillary artery, the orifice of the right subclavian artery was covered with a stent-graft inserted into the right common carotid artery-brachiocephalic artery and the right subclavian artery was occluded with coils distal to the aneurysm. Post operation angiogram showed complete exclusion of the SCAA and patency of the right common carotid and right vertebral artery. We thought this hybrid treatment for the intrathoracic SCAA could be a useful surgical strategy.