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As a result, psychiatrists should systematically rule out the presence of a comorbid depressive disorder and not simply assume that depressive symptoms result from alcohol use or its psychosocial consequences. Whereas full-time employment appears to be a protective factor in alcoholics, factors that increase suicide risk include communications of suicidal intent, prior suicide attempts, continued or heavier drinking, recent unemployment, living alone, poor social support, legal and financial difficulties, serious medical illness, other psychiatric disorders, personality disturbance, and other substance use (64, 149, 152, 154, 156, 158, 159). In terms of gender, alcoholic men are more likely to die by suicide, but female alcoholics appear to have a greater standardized mortality due to suicide than men (64), indicating an increased risk of suicide in alcoholics regardless of gender. While the likelihood of a suicidal outcome increases with the total number of risk factors (149, 160), not all of these factors suggest an immediate risk. In addition to being associated with an increased risk of suicide, alcohol use disorders are associated with a greater likelihood of suicide attempts (162, 163). Thus, individuals with alcohol use disorders are at increased risk for suicide attempts as well as for suicide. Family histories of alcoholism and comorbid psychiatric disorders, particularly mood disorders and other substance use disorders, are frequent in alcoholics who die by suicide and who attempt suicide. Interpersonal loss and other adverse life events are commonly noted to precede suicide in alcoholics. These factors may act as precipitants, or, conversely, alcohol use disorders may have a deteriorating effect on the lives of alcoholics and culminate in suicide. Together, however, these findings suggest the need to identify and address comorbid psychiatric diagnoses, family history, and psychosocial factors, including recent interpersonal losses, as part of the suicide assessment of persons with alcohol use disorders. Substance use disorders are particularly common among adolescents and young adults who die by suicide (110, 145, 173, 174). In fact, it has been suggested that the spread of substance abuse may have contributed to the two- to fourfold increase in youth suicide since 1970 (147). For many individuals, substance abuse and alcoholism are co-occurring, making it difficult to distinguish the contributions of each to rates of suicide (153, 172, 173). Substance use disorders also seem to make an independent contribution to the likelihood of making a suicide attempt (176, 177). Even after other factors, including comorbid psychiatric disorders and demographic characteristics, are controlled, it is the number of substances used, rather than the type of substance, that appears to be important (176). As with suicide in individuals with alcohol use disorders, the loss of a significant personal relationship is a common precipitant for a suicide attempt (179). Suicide attempts are also more likely in individuals with substance abuse who also have higher childhood trauma scores for emotional neglect (180, 181). Moreover, a substance use disorder may complicate mood disorders (182), increasing susceptibility to treatment resistance, increasing psychological impairment, and contributing to an elevated risk for suicide attempts. Thus, it is important to identify patterns of substance use during the psychiatric evaluation and to note comorbid psychiatric diagnoses or psychosocial factors that may also affect the likelihood of suicidal behaviors among individuals with substance use disorders. Compared with the general population, individuals with personality disorders have an estimated risk for suicide that is about seven times greater (64). Specific increases in suicide risk have been associated with borderline and antisocial personality disorders, with possible increases in risk associated with avoidant and schizoid personality disorders (186). Psychological autopsy studies have shown personality disorders to be present in approximately one-third of those who die by suicide (174, 183, 186, 187). Among psychiatric outpatients, personality disorders are present in about onehalf of patients who die by suicide (78, 188). In individuals with personality disorders, suicide risk may also be increased by a number of other factors, including unemployment, financial difficulty, family discord, and other interpersonal conflicts or loss (189, 190). In individuals with borderline personality disorder, in particular, impulsivity may also increase suicide risk (185). Although comorbid diagnoses do not account for the full increase in suicide risk with personality disorders (184, 185), comorbid diagnoses are frequent and augment suicide risk. In fact, for individuals with personality disorders, concurrent depressive symptoms or substance use disorders are seen in nearly all individuals who die by suicide (187).

Residency is an essential dimension of the transformation of the medical student to the independent practitioner along the continuum of medical education. It is physically, emotionally, and intellectually demanding, and requires longitudinally-concentrated effort on the part of the resident. The specialty education of physicians to practice independently is experiential, and necessarily occurs within the context of the health care delivery system. Developing the skills, knowledge, and attitudes leading to proficiency in all the domains of clinical competency requires the resident physician to assume personal responsibility for the care of individual patients. For the resident, the essential learning activity is interaction with patients under the guidance and supervision of faculty members who give value, context, and meaning to those interactions. As residents gain experience and demonstrate growth in their ability to care for patients, they assume roles that permit them to exercise those skills with greater independence. This concept-graded and progressive responsibility-is one of the core tenets of American graduate medical education. Orthopaedic surgery includes the study and prevention of musculoskeletal diseases, disorders, and injuries, and their treatment by medical, surgical, and physical methods. Institutions Sponsoring Institution One sponsoring institution must assume ultimate responsibility for the program, as described in the Institutional Requirements, and this responsibility extends to resident assignments at all participating sites. On average, there must be at least four hours of formal teaching activities each week. The program director should continue in his or her position for a length of time adequate to maintain continuity of leadership and program stability. Other qualified and properly credentialed practitioners may participate in the education of residents as determined by the program director. The physician faculty must possess current medical licensure and appropriate medical staff appointment. There should be institutional support for a full-time equivalent orthopaedic surgery program coordinator designated specifically for orthopaedic surgical education. Electronic medical literature databases with search capabilities should be available. Residents must have Internet access to appropriate full-text journals and electronic medical reference resources for education and patient care at all participating sites. Eligibility Criteria the program director must comply with the criteria for resident eligibility as specified in the Institutional Requirements. The program director may not appoint more residents than approved by the Review Committee, unless otherwise stated in the specialty-specific requirements. Competency-based goals and objectives for each assignment at each educational level, which the program must distribute to residents and faculty at least annually, in either written or electronic form; (Core) Regularly scheduled didactic sessions; (Core) Basic science education and the principal clinical conferences should be provided at the primary clinical site. Evaluation Resident Evaluation the program director must appoint the Clinical Competency Committee. Resident Duty Hours in the Learning and Working Environment Professionalism, Personal Responsibility, and Patient Safety Programs and sponsoring institutions must educate residents and faculty members concerning the professional responsibilities of physicians to appear for duty appropriately rested and fit to provide the services required by their patients. Residents and faculty members must demonstrate an understanding and acceptance of their personal role in the following: assurance of the safety and welfare of patients entrusted to their care; (Outcome) provision of patient- and family-centered care; (Outcome) assurance of their fitness for duty; (Outcome) management of their time before, during, and after clinical assignments; (Outcome) recognition of impairment, including illness and fatigue, in themselves and in their peers; (Outcome) attention to lifelong learning; (Outcome) the monitoring of their patient care performance improvement indicators; and, (Outcome) honest and accurate reporting of duty hours, patient outcomes, and clinical experience data. Other portions of care provided by the resident can be adequately supervised by the immediate availability of the supervising faculty member or resident physician, either in the institution, or by means of telephonic and/or electronic modalities. When available, evaluation should be guided by specific national standards-based criteria. Teamwork Residents must care for patients in an environment that maximizes effective communication. This must include the opportunity to work as a member of effective interprofessional teams that are appropriate to the delivery of care in the specialty. Resident Duty Hours Maximum Hours of Work per Week Duty hours must be limited to 80 hours per week, averaged over a four-week period, inclusive of all in-house call activities and all moonlighting. Strategic napping, especially after 16 hours of continuous duty and between the hours of 10:00 p. Residents may be allowed to remain on-site in order to accomplish these tasks; however, this period of time must be no longer than an additional four hours. While it is desirable that residents in their final years of education have eight hours free of duty between scheduled duty periods, there may be circumstances when these residents must stay on duty to care for their patients or return to the hospital with fewer than eight hours free of duty.

The approval was based on cumulative data from two clinical trials that showed that about 20 percent of patients had a complete response following treatment with Inqovi (382) (383). Rare cancers pose significant challenges to many stakeholders in the cancer community, including patients, physicians, and researchers. Together, rare cancers account for about 27 percent of cancer cases and about 25 percent of cancer deaths each year in the United States. Rare cancers can be challenging for researchers to study and for physicians to treat (see sidebar on the Challenges Posed by Rare Cancers, p. The founding members were subsequently joined by the French National Cancer Institute, the Canadian Clinical Trials Group, the Japan Clinical Oncology Group, and the Clinical Oncology Society of Australia. I was told that I had two options: radical amputation of my whole left shoulder or enroll in a clinical trial testing an oral medication called tazemetostat (Tazverik). The cancer is under control, I have far less pain than I used to , and I have regained some use of my left arm. I eventually went to my primary care physician who referred me for physical therapy. I had physical therapy for several months, but the pain continued to get worse and worse. It turned out that this is a rare type of cancer; the doctors had to send the biopsy to a hospital in Boston to get confirmation of the diagnosis. At my worst, the pain in my shoulder was so great that I could not use my left arm. I had to hold my left arm up with my right hand and I had to learn to write with my right hand because I am a leftie. When my oncologist gave me the diagnosis, he brought a whole team with him to explain my treatment options, a surgeon, a nurse practitioner, and a clinical trial coordinator. He pointed to the bump on my neck and said he would have to go and take my whole shoulder out. Then, the clinical trial coordinator told me the alternative was a clinical trial testing a new treatment. For that, I would have to take eight tablets a day, four in the morning and four in the evening. My oncologist says that this is called a partial response and it is a win for patients with epithelioid sarcoma. My husband takes care of me, two of my sisters each gave up time to stay with me, another sister flies with me to my oncologist appointments; and my neighbor drove me to my appointments for a year. It was hard at first to accept that I needed so much help, but I am so grateful to all of them. My experience has taught me that I am a lot stronger than I thought I was, but I could not have done it without the support of my family and friends. Avapritinib (Ayvakit) is a new molecularly targeted therapeutic that can block the effects of D842V mutations. Tenosynovial giant cell tumors are a group of rare tumors that arise in and around the joints and tendons (391). These tumors are benign, but they cause damage to the joints, which leads to pain, swelling, and limitation of movement of the joint. If patients do not have surgery or if the tumor continually recurs, patients suffer damage and degeneration of the affected joint and surrounding tissues or structures. The immune cells that accumulate form the bulk of the tumor and cause damage to surrounding tissue. Pexidartinib was the first molecularly targeted therapeutic approved specifically for treating tenosynovial giant cell tumors. In April 2020, patients with another rare type of cancer, cholangiocarcinoma, or bile duct cancer, also gained a first molecularly targeted therapeutic treatment option, pemigatinib (Pemazyre). Cholangiocarcinoma arises in cells that form the bile ducts, which are small tubes that connect the liver and gallbladder to the small intestine. There are two forms of the disease, named depending on whether the bile ducts in which the cancer begins are inside (intrahepatic cholangiocarcinoma) or outside (extrahepatic cholangiocarcinoma) the liver.

Kalanikupule and some of his men escaped capture and fled to O`ahu after the battle. He was forced to abandon his pursuit of complete victory over the Maui kingdom and returned to Hawai`i to deal with his sole remaining archrival for control of Hawai`i island. The islands of Maui and Molokai were later reclaimed without incident by the combined forces of an avenging Kahekili and his brother Ka`eo, King of Kaua`i, Ralph S. The two leeward Kings then prepared to launch an invasion against Kamehameha from Maui. Before Kamehameha returned from his leeward campaign, he sent one of his chiefs to consult with a renowned kilokilo (seer) resident on the island of O`ahu "to find out by what means he could make himself master of the whole of Hawaii island. It was an enormous task that involved the physical labor of not just his people, but also Kamehameha himself. His attention, though, would soon be diverted to the invading force of the two leeward Kings departing from Maui. Kahekili and Ka`eo embarked from Maui on a large fleet of canoes and invaded the northern coast of Hawai`i committing "serious depredations before Kamehameha could interpose to stop them. The invading force was engaged in a naval battle, "and when the two fleets came together not 36 Kuykendall, supra note 34, 36. Unification of the Kingdom of Hawai`i Refocusing his attention on the prophesy, Kamehameha returned to labor at Pu`ukohola and the great temple was finally completed and consecrated with full religious rites in the summer of 1791. Thereafter, with an undeterred vision of consolidating his dominion over the fractured Hawai`i island kingdom, he sent two of his Chiefs, Keaweaheulu and Kamanawa, to meet with Keoua. Keoua was killed before he could set foot on the shoreline fronting the grand temple. Kamehameha "devoted the next few years to works of peace, the organization and administration of his government, and the normal development of the resources of his 40 Kuykendall, supra note 34, 37. By order of the British Admiralty, Captain Vancouver was to complete the exploration of the northwest coast of the American continent begun by the late Captain James Cook. In 1778, Cook named the island group the Sandwich Islands in honor of his superior the First Lord of the British Admiralty, John Montagu, 4th Earl of Sandwich. Captain Vancouver was on good terms with all three kingdoms and even attempted to broker peace between them, but it was with Kamehameha that a close relationship developed. Kamehameha and Captain Vancouver became close friends and an affinity soon developed between the Hawai`i King and the British. According to Hopkins, Kamehameha also "requested of Vancouver that on his return to England he would procure religious instructors to be sent to them from the country of which they now considered themselves subjects. George Vancouver, Voyage of Discovery to the North Pacific Ocean and the round the World, vol. His son, Kalanikupule, "was recognized as the Moi [King] of Maui and its dependencies, Lanai, Molokai, and Oahu. This arrangement of a shared kingdom became a source of tension between the Kaua`i and Maui chiefs and a battle later took place on O`ahu between the two factions. While Ka`eo, with an army of soldiers, prepared to depart from the leeward side of O`ahu to his Kingdom of Kaua`i, a plan was contrived by his chiefs to overthrow Kalanikupule at Waikiki and bring the entire leeward islands under Kaua`i rule. The two armies met on the plains of Honolulu just above Pearl Harbor, and with the assistance of two British ships, the Jackall and the Prince Lee Boo commanded by Captain Brown, Kalanikupule defeated the invaders and Ka`eo was killed in battle in December of 1794. The success of the battle soon had Kalanikupule and his chiefs entertaining ideas of avenging their defeat at the hands of Kamehameha four years earlier, and they prepared for an invasion of the Kingdom of Hawai`i. According to Kuykendall: Success inflated the ambition of Kalanikupule and his chiefs and they began to dream of conquering Kamehameha. A cunning plot was formed and on the first day of January, 1795, the Jackall and the Prince Lee Boo were captured, the two captains, Brown and Gordon, were killed, and the surviving members of the crews were made prisoners. In February of 1795, Kamehameha departed Hawai`i with an army of 16,000 men and quickly overran Maui, Lanai and Molokai. The defeat of the Maui kingdom rendered Kamehameha master of Hawai`i, Maui, Lanai, Molokai and O`ahu. By April of 1810 the Sandwich Islands came under the complete control and dominion of one king after the Kingdom of Kaua`i and its dependency, the island of Ni`ihau, was voluntarily ceded by Kaumuali`i who thereafter recognized Kamehameha as his liege and lord. Kaumuali`i was permitted to govern Kaua`i with his own chiefs, but paid an annual tribute to Kamehameha as his feudatory lord.