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(Case presenter) A 90yearold woman visited our hospital because of appetite loss for the last 2 weeks. The patient lived in a nursing care house, had good communication with caregivers, with retained basic daily activities. She had a good appetite until 2 weeks before, when she became unable to consume only half of her breakfast and most of her lunch and dinner. Besides, she was able to consume as less as 700 ml of water per day. She also complained of fatigue and headache. The nursing care staff admitted that she had bowel movements approximately every 3 days. One week before, the patient visited another hospital and underwent a brain magnetic resonance imaging scan, which only revealed evidence of a previous ischemic stroke. The patient was dozing all day for the last few days, and finally, she was brought to our hospital for further evaluation. (Discussant) Appetite loss in older people is a frequent problem in primary care, and differential diagnoses must be considered across the biopsychosocial spectrum (see Table 1). Any disorder in the pathway of food can cause anorexia: oral disorders including caries, stomatitis, denture incompatibility, and lack of hygiene care; difficulty in swallowing including neurological disorder and sarcopenia; esophageal and gastric disorders including cancer, ulcer, and motility disorder; and intestinal disorder including obstruction such as constipation. Feeding may be disturbed by various conditions including taste or smell disorder, a decreased amount of saliva, upper limb dysfunction, inappropriate seated position, and visual disturbance. Progressive cognitive decline, depression, paranoia, and inappropriate feeding assistance may also prevent sufficient feeding. A wide range of systemic conditions can cause anorexia: infectious diseases including pneumonia, pyelonephritis, cholecystitis, and other systemic infection; noninfective inflammatory diseases; cancers and lymphomas; debilitating conditions including chronic heart failure, chronic pulmonary diseases, neurodegenerative disorders, and rheumatic diseases; electrolyte disturbance including sodium, potassium, magnesium, and calcium abnormalities; and endocrinopathy including hyperor hypoglycemia, thyroid disorders, and adrenal disorders. The persistence of only decreased appetite in the course of 2 weeks reduces the possibility of acute systemic inflammatory diseases, while I would not rule out the possibility of insidious inflammatory diseases such as tuberculosis and malignant neoplasms. Polymyalgia rheumatica and vasculitis would not be highly suspected because of the patient's age. Debilitating conditions should be scrutinized, while there are no specific findings so far. Electrolyte, metabolic, and endocrine disorders would be excluded from laboratory testing: these disorders have a wide variety of clinical manifestations and often have clinical expressions that are not apparent at first glance. Being seated during feeding may be intolerable for patients in this age group with orthostatic hypotension as a result of synucleinopathies, peripheral neuropathies, and agerelated baroreceptor dysfunction. In older patients who cannot complain of pain, loss of appetite can be a trigger for finding a bone fracture. All older patients with appetite loss should have their prescription reviewed. Agents affecting the central nervous system, including anticonvulsants, antipsychotics, benzodiazepines, and opiates, sometimes cause anorexia in older patients. Digoxin, levodopa, and theophylline also cause anorexia directly. Depression may cause anorexia, and selective serotonin reuptake inhibitors may also cause nausea, diarrhea, and anorexia. Many other drugs can cause secondary anorexia. For example, anticholinergics may cause dry mouth and delirium, leading to appetite loss.

(Case presenter) A 90-year-old woman visited our hospital because of appetite loss for the last 2 weeks. The patient lived in a nursing care house, had good communication with caregivers, with retained basic daily activities. She had a good appetite until 2 weeks before, when she became unable to consume only half of her breakfast and most of her lunch and dinner. Besides, she was able to consume as less as 700 ml of water per day. She also complained of fatigue and headache. The nursing care staff admitted that she had bowel movements approximately every 3 days. One week before, the patient visited another hospital and underwent a brain magnetic resonance imaging scan, which only revealed evidence of a previous ischemic stroke. The patient was dozing all day for the last few days, and finally, she was brought to our hospital for further evaluation.
(Discussant) Appetite loss in older people is a frequent problem in primary care, and differential diagnoses must be considered across the bio-psycho-social spectrum (see Table 1). Any disorder in the pathway of food can cause anorexia: oral disorders including caries, stomatitis, denture incompatibility, and lack of hygiene care; difficulty in swallowing including neurological disorder and sarcopenia; esophageal and gastric disorders including cancer, ulcer, and motility disorder; and intestinal disorder including obstruction such as constipation. Feeding may be disturbed by various conditions including taste or smell disorder, a decreased amount of saliva, upper limb dysfunction, inappropriate seated position, and visual disturbance. Progressive cognitive decline, depression, paranoia, and inappropriate feeding assistance may also prevent sufficient feeding.  The patient was prescribed various kinds of drugs, but their side effects may not be regularly checked. High doses of iron had been prescribed for a long time, probably for anemia. If the patient's anemia was caused by iron deficiency, it might have already been corrected.
Platelets usually increase in iron deficiency anemia, which was also not consistent with this case. The patient's anemia was surely not caused by iron deficiency, but to another condition such as known cirrhosis or other etiologies. Iron preparation may cause gastrointestinal symptoms. Potassium can also cause dysphagia. This patient's potassium level was not checked regularly, and it was probable that this prescription was potentially inappropriate.
Eldecalcitol and magnesium oxide were prescribed to the patient by different doctors. Activated vitamin D3 agents are effective in preventing osteoporotic fracture, but long-term use may cause hypercalcemia because vitamin D enhances intestinal calcium absorption and bone mobilization. Vitamin D-induced hypercalcemia is quite common in Japan. Hypercalcemia leads to arteriole vasoconstriction and then decreases renal blood flow and glomerular filtration rate. Hypercalcemia also suppresses parathyroid hormone (PTH) secretion and then increases bicarbonate reabsorption. If hypovolemia occurs because of general fatigue and altered mental status caused by hypercalcemia, the kidney injury and metabolic alkalosis are maintained and worsened. The risk of drug-induced hypercalcemia is thus high in older age and chronic kidney disease.
The combination of vitamin D and magnesium oxide makes the risk of hypercalcemia much higher. Magnesium ions, which are divalent cations as calcium ions, stimulate the calcium-efficient sensing receptors and suppress PTH secretion. Magnesium oxide also causes mild alkalemia because of the following pathway. Magnesium oxide is converted to magnesium chloride in the stomach by gastric acid (hydrochloric acid). Magnesium chloride is then converted to magnesium bicarbonate and magnesium carbonate in the intestine by pancreatic juice (sodium bicarbonate). Finally, intestinal absorption of bicarbonate leads to alkalemia. Therefore, the calcium level should be examined in this patient.
(Case presenter) The patient was seated in a wheelchair and looked lethargic. The patient opened her eyes by calling out. She did not say few words. The vital signs were as follows: body temperature was 36.7°C, blood pressure 160/68 mm Hg, heart rate 60 beats per minute, respiratory rate 16 per minute, and oxygen saturation 97% with ambient air. The conjunctiva was no pallor. There was dryness of the mouth. The jugular vein was not distended. A II/VI systolic ejection heart murmur was heard over the second right sternal border. The lung sounds were clear. The abdomen was flat, soft, and not tender. There was no hepatosplenomegaly or lymphadenopathy.
Edema was not appreciated in the limbs. No limb abnormal movement was seen. Deep tendon reflexes were normal. Joints, skin, and neurologic examination were normal. Bruits over the carotid arteries, abdominal aorta, renal arteries, and common iliac arteries were not heard. Tenderness was not seen over the muscles in the limbs. Hypernatremia usually occurs in patients who are unable to drink water on their own. The patient took only about 700 ml of water for the last several days and was at high risk of free water depletion.
It was possible that anorexia occurred for some reason and was further aggravated by hypovolemia and dehydration. Long-term discharged on the day 20, and hypercalcemia did not recur since then.

| DISCUSS ION
The patient developed hypercalcemia as a result of inappropriate medication. The patient was old aged and had chronic kidney disease and should have undertaken regular checkups of serum calcium level during the medication of an activated vitamin D3 agent. It is reported that more than half of older patients do not have a specific disease that corresponds directly to the symptoms and signs presented. 9 Physicians should be aware that a symptom and a disease do not always have a one-to-one correspondence in older adults, and the cumulative effects of patients' bio-psycho-social factors should be scrutinized.
The patient regularly saw three doctors. The doctors did their practice according to their own specialties, but each care was not coordinated. No one was in charge of the whole part of her daily living and health maintenance. That is, her medical care was fragmented. Fragmentation was defined as "focusing and acting on the parts without adequately appreciating their relation to the evolving whole." 10 Even if each professional does the best for a patient, fragmentation of care sometimes has the unintended consequence of making things worse: each care may become inefficient, ineffective, inequal, antiprofessionalized, and deindividualized. 10 Instead, integrated care maximizes patients' opportunities for health and healing.
Care integration against fragmentation is one of the key roles of primary care professionals in today's health care systems.
In summary, we describe the case of hypercalcemia caused by new-type calcium-alkali syndrome. Polypharmacy and adverse drug events are common in older patients, and individualized approaches are needed. Clinical reasoning in older patients often requires considering the cumulative effects of bio-psycho-social factors. Primary care professionals are expected to have an important role in integrating patients' health care against fragmentation.

ACK N OWLED G M ENTS
None.

CO N FLI C T O F I NTE R E S T
The authors have stated explicitly that there are no conflicts of interest in connection with this article.