Personal experience, posttraumatic symptomatology, and meaning in life during the first months of the COVID-19 pandemic.

The traumatic subjective distress and personal meaning in life were examined in the context of the first months of the COVID-19 pandemic sanitary crisis and home lockdown. METHOD: A total of 543 participants answered an online survey that included questions about the individual characteristics of the pandemic experience, the Impact of Event Scale-Revised, and the Personal Meaning Profile-Brief. RESULTS: Nearly all of life impaired areas, having the suspicion of being ill with COVID-19, having lost a close person to this virus, and having been accompanied during the lockdown were experiences associated with higher PTSD symptoms. Posttraumatic symptomatology was inversely correlated with areas of meaning in life. Lastly, a higher number of affected areas and a negative subjective lockdown circumstance explained greater total PTSD symptoms. CONCLUSION: Specific pandemic experiences and lockdown circumstances affected the presence of posttraumatic symptoms. The personal meaning of life seems to be involved in the process of less adverse traumatic consequences.

[Drug therapy follow-up in patients admitted to a Surgery Department]. / Seguimiento del tratamiento farmacológico en pacientes ingresados en un Servicio de Cirugía.

INTRODUCTION: Patients admitted to surgery departments receive multiple drugs before, during and after surgical procedures. Anti-infectious therapy, anesthetics, anti-embolic agents, and analgesics stand out amongst others. Our objective was to implement pharmacotherapeutic follow-up as a means to detect, prevent, and solve medication-related problems (MRPs) in inpatients, and to establish consensus strategies to solve avoidable MRPs. MATERIAL AND METHODS: An observational prospective study of 22 patients hospitalized in a Surgery Department, Hospital Infanta Margarita, Cabra (Córdoba) was conducted. Dader methodology was adapted for drug therapy follow-up in the hospital setting. RESULTS: In all, 108 MRPs were detected; 22.04% were associated with medication needs (MRP1:13.6% and MRP2: 8.5%), 40.68% with ineffectiveness (MRP3: 22.0% and MRP4: 18.6%), and 37.28% with lack of safety (MRP5: 10.2% and MRP6: 27.1%). Out of 108 MRPs found, 64 (59.3%) were avoidable; 97 pharmaceutical interventions were carried out (89.8% of cases), acting in 63 (58%) MRPs detected in cooperation with physicians, while 46 MRPs were solved (42%). We found 1 MRP in each 2.6 patients -- admission days, and 1 MRP per 4.5 patients -- admission days occurred after pharmaceutical intervention during the study period. CONCLUSIONS: The use of pharmacotherapeutic follow-up in patients admitted to this department has improved the quality of health care.

Developmental instability and schizotypy.

INTRODUCTION: It has been suggested that evidence of developmental disturbance of cognition and lateralisation in schizophrenia can be best understood from the perspective of developmental stability (DS), an indicator of the extent to which an individual develops according to a specified ontogenic programme in the presence of environmental noise. Higher levels of fluctuating asymmetry (FA; the difference between right and left side of a quantitative morphological trait such as dermatoglyphics) are thought to reflect less DS. We examined this issue for dimensions of schizotypy. METHODS: Associations between FA, measures of laterality and cognitive function on the one hand, and negative and positive dimensions of schizotypy on the other, were examined in a sample of 260 healthy adolescents aged 11.9-15.6years. FA was measured as a-b ridge count right-left differences. Neuropsychological measures yielded a general cognitive ability score and a frontal function score. Laterality was assessed with the Annett scale. RESULTS: Measures of psychosis proneness were normally distributed. Negative schizotypy was associated with more FA and lower general cognitive ability in a dose-response fashion. The association with FA was more apparent in boys. No associations existed with laterality or frontal function. CONCLUSION: The negative dimension of schizotypy may be associated with early developmental instability, resembling the pattern seen in the negative symptom dimension of schizophrenia. Measures of fluctuating asymmetry may be more sensitive with regard to the schizotypy phenotype than measures of laterality.

Neurological soft signs in adolescents with poor performance on the continous performance test: markers of liability for schizophrenia spectrum disorders?

There is much evidence that neurological soft signs (NSS) are highly prevalent in both adults and children with schizophrenia. In addition, they have been detected as early precursors of a schizophrenic outcome in at-risk subjects. Such findings point to the possible value of NSS as neurointegrative markers in schizophrenia which has been hypothesized to be a neurodevelopmental disease. In our study we used a biobehavioral criterion to select the 'at-risk' group, a sustained attentional deficit as measured by the continuous performance test (CPT). We compared 140 normal adolescents with 162 'CPT-linked vulnerable' adolescents (index subjects) on a battery for the assessment of NSS (including laterality), IQ, frontal lobe function and schizotypy. An association was found between NSS and attentional deficit. Furthermore, index subjects with NSS were characterized by lower IQ scores, poorer performance on frontal lobe tests and greater problems with social interaction. There was also a trend for an association between male sex and both left-handedness and NSS.

Transient cerebral dysfunction secondary to high-dose methotrexate.

A transient acute neurologic syndrome occurred in 22 patients receiving high-dose methotrexate (HDMTX) (8 to 9 g/m2) for a variety of malignancies. The neurologic signs were similar in all cases. The syndrome occurred an average of six days after the second or third weekly treatment. Common findings included behavioral abnormalities, focal sensorimotor signs, and abnormal reflexes. Signs often alternated from one side to the other. Evaluations including computed tomography (CT) scan, lumbar puncture, hemogram, and blood chemistry were normal. The EEG revealed some slowing in all cases. The cause of this syndrome is unknown. It is transient and usually does not recur. Its appearance does not preclude further treatment with HDMTX.

Redefined role of radiation in combined treatment of Ewing's sarcoma.

Eighty-six patients with Ewing's sarcoma were analyzed as to the role of radiation therapy. Fifty-eight patients (P group) had removal of the involved part of the bone after preoperative chemotherapy, and 28 (NP group) had local treatment either at the same time or before chemotherapy. Thirty-six of 58 P-group patients (61%) and 13 of the 28 NP-group patients (48%) are alive. Five of 48 patients in P-group, who had postoperative radiation, had local recurrence, as did 6 of 11 without postoperative radiation, a statistically significant difference (p = 0.001).

Semiquantitative gallium scintigraphy in patients with osteogenic sarcoma.

Sequential gallium scans were performed in 37 patients with newly diagnosed osteogenic sarcoma. High gallium uptake was found more often in males in the 10 to 19 age group and in femoral lesions. High uptake was also seen in patients who had predominantly osteoblastic or mixed changes on radiographs and in those who had a soft tissue mass. Following chemotherapy, significant decrease of tumor to nontumor ratio occurred in the patients who responded to treatment as shown by a Grade III or IV response on histologic examinations at the time of en bloc resection. It is concluded that semiquantitative gallium scintigraphy is useful in monitoring therapeutic response in patients with osteogenic sarcoma.

Primary osteogenic sarcoma of the femur: a model for the use of preoperative chemotherapy in high risk malignant tumors.

The value of adjuvant chemotherapy in primary osteogenic sarcoma (OSA) is still considered controversial by some. One reason may be that various reported series include patients with widely varying prognostic variables. To address this, the effect of chemotherapy on the continuous disease-free (CNED) survival was analyzed in 100 patients aged 21 yr or less with OSA of the femur. This classically poor prognostic group of patients represented 51% of all primary OSA seen at the Memorial Sloan-Kettering Cancer Center during the study interval. This study includes all patients aged 21 yr or less with fully malignant (Grade III-IV/IV) OSA of the femur and no metastases treated from November 1973 through November 1981. The first (T-4) protocol (31 patients) consisted of high dose methotrexate (HDMTX) with leucovorin rescue, cyclophosphamide (Cyc), and adriamycin. In the second (T-7) protocol (23 patients) the dose of HDMTX was increased to 12 g/m2 for prepubescent patients, and bleomycin, Cyc, and dactinomycin replaced Cyc. The current (T-10) protocol (46 patients) uses the same CT as T-7, but patients not having a complete response of the primary tumor to preoperative CT receive additional cisplatinum (120 mg/m2) with adriamycin (30 mg/m2/day for two consecutive days). In 31 patients treated with T-4 the CNED survival was 32% with a minimum follow up of over 7 yr. On T-7, 15/23 patients with femur primaries had a CNED survival of 65% with all of the surviving patients followed for more than 5 yr. The addition of cisplatinum in T-10 has resulted in CNED survival rate of 77% in 34/44 patients (excluding two patients that died CNED during and after treatment); the median follow-up patients who are alive CNED is 33 months, with a minimum of 2 yr follow up on the last patient entered.

Pelvic Ewing's sarcoma. Advances in treatment.

In a study of eighteen patients with pelvic Ewing's sarcoma who were treated with a multidisciplinary approach, chemotherapy was effective in controlling systemic spread of the tumor. Surgery coupled with improved methods of chemotherapy provided results that were statistically superior to those obtained with radiation and chemotherapy alone in control of the local pelvic lesion. A twofold increase in the survival rate was seen at a median follow-up of thirty-six months in the patients who had the resection. Our results suggest that pelvic Ewing's sarcoma is best treated by initial chemotherapy, followed by local wide marginal resection of the pelvic lesion coupled with perimeter radiation therapy and concluded with additional chemotherapy. Survival rates of patients with pelvic Ewing's sarcoma may then approach the excellent survival rates of patients with lesions in more favorable anatomical locations.

Chemotherapy of malignant fibrous histiocytoma of bone. A report of five cases.

Five patients with evaluable malignant fibrous histiocytoma (MFH) of bone (three with primary tumor and two with primary tumor and metastatic disease) were treated with preoperative chemotherapy including high dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) as is used for patients with osteogenic sarcoma. All five patients demonstrated a clinical response to chemotherapy. Three of four patients who underwent surgery had complete responses and one patient had greater than 90% tumor necrosis as documented by histologic examination of the resected primary tumor. All four patients who underwent surgery following preoperative chemotherapy are surviving free of disease from one to six years from the start of treatment; chemotherapy was discontinued after six to 11 months in these patients. The median disease-free survival time is 31.5 months. This study demonstrates the effectiveness of chemotherapy in MFH of bone, and in particular the effectiveness of HDMTX with CFR which caused measurable responses in all patients while receiving this therapy as a single agent.

Primary osteogenic sarcoma: eight-year experience with adjuvant chemotherapy.

Since October 1973, 185 patients 21 years of age or younger with primary osteogenic sarcoma of an extremity were treated with adjuvant chemotherapy. Twenty-five of the first fifty-two patients (48%) have remained free of disease for a median of 7 years. In the next chemotherapy protocol most patients had chemotherapy prior to amputation or resection, during which time the dose of high-dose methotrexate was escalated in many patients to that needed to shrink the primary tumor. For a median of 4 years 43 of 54 patients (80%) have remained free of disease. In the current protocol, the response of the primary tumor to chemotherapy with high-dose methotrexate was used to select postoperative adjuvant chemotherapy for the patient. With the latter approach 73 of 79 patients (92%) have remained continuously free of disease for a median of 2 years. This experience demonstrates the value of chemotherapy in increasing the cure rate in osteogenic sarcoma and that the response to preoperative chemotherapy can help select postoperative chemotherapy to produce an even higher potential cure rate for osteogenic sarcoma.

Chemical pleuritis as the cause of acute chest pain following high-dose methotrexate treatment.

This report describes the clinical and roentgenographic features of a pleuritis seen following the administration of high-dose methotrexate (HDMTX). Among 210 patients who received 3130 courses of HDMTX from 1977 through 1980, the incidence of this clinical entity was 8.5% (n = 18). The sudden onset of chest pain occurred only after the third or fourth HDMTX treatment and usually lasted between three and five days; the pain was often quite severe and led to extensive clinical examination before recognition of the benign transient nature of this syndrome. Roentgenographic examination of the chest revealed thickening of the intralobar pleura, most prominent on the right side. Our observations support the hypothesis that this adverse drug reaction occurs more frequently than assumed, but is often ignored or misinterpreted.

Radiographic changes in primary osteogenic sarcoma following intensive chemotherapy. Radiological-pathological correlation in 63 patients.

Sixty-three patients with osteogenic sarcoma of the long bones, all of whom were treated with chemotherapy, demonstrated striking and unusual radiographic changes. Patients with a "good" radiographic response (48%) showed the most dramatic changes, including medullary sclerosis, prominent periosteal new bone formation, and disappearance of the soft-tissue mass; and these findings correlated well with the histological grading of the surgical specimens. Radiographic evaluation of patients receiving chemotherapy for osteogenic sarcoma is a valuable method of assessing response.

Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy.

Since June 1978, 57 patients with primary osteogenic sarcoma of an extremity were treated with high-dose methotrexate (HDMTX) and citrovorum factor rescue (CFR), Adriamycin, and the combination of bleomycin, cyclophosphamide and dactinomycin (BCD) given for 4-16 weeks prior to definitive surgery. Histologic examination of the resected primary tumor determined the effect of preoperative chemotherapy with many primary tumors showing greater than 90% tumor necrosis attributable to preoperative chemotherapy. All patients having this favorable effect of chemotherapy on the primary tumor were continued on the same chemotherapy regimen postoperatively (regimen B). However, in those patients not having a good effect of preoperative chemotherapy on the primary tumor, HDMTX with CFR was subsequently deleted from their postoperative chemotherapy and they were placed on a regimen containing cisplatinum at the dose of 120mg/M2 with mannitol diuresis combined with Adriamycin in addition to BCD (regimen A). In the current study, 35 of the 57 patients did not demonstrate a good effect of chemotherapy on the primary tumor and were assigned to regimen A postoperatively. Of these 35 patients, 32 (91%) have remained continuously free of recurrent or metastatic disease from 6-34 months following the start of therapy. Among the 22 remaining patients having a good histologic response and treated with regimen B postoperatively, there has been only one relapse in a patient who had a local recurrence in the area of an inadequately resected primary tumor three months after the cessation of chemotherapy. Thus, 53 of 57 patients (93%) are continuously with no evidence of recurrent or metastatic disease from 6-35 months (median, 20 months) from the start of treatment. This study demonstrates the value of thorough histologic examination in predicting survival in responding patients and in helping identify patients whose disease-free survival rate can be substantially increased if they are given alternative postoperative adjuvant chemotherapy after failing to have a good response to preoperative chemotherapy. This individualized chemotherapeutic strategy has yielded the highest disease-free survival rate reported to date for osteogenic sarcoma.

Embryonal rhabdomyosarcoma of the middle ear presenting as sarcoma botryoides. Favorable outcome in a 12-year-old boy.

A 12-year-old boy presented with a history of earache, fever and granuloma of the auditory canal. Biopsy revealed embryonal rhabdomyosarcoma. The patient was treated with chemotherapy and radiation therapy, which led to complete disappearance of the tumor without recurrence after three years. Diagnosis, staging and timing of the treatment plan is discussed for this rare but highly malignant tumor.

Ewing's sarcoma: ten-year experience with adjuvant chemotherapy.

Since May 1970, 67 consecutive patients with primary (nonmetastatic) Ewing's sarcoma were treated with adjuvant chemotherapy (CT) in addition to radiation therapy (RT) or surgery for the primary tumor. The first 19 patients were treated with four-drug sequential CT (T-2). The second protocol was a seven-drug induction combination CT (T-6) followed by T-2 maintenance CT; in both protocols CT was continued for 18 months. The current protocol (T-9) consists of combination CT given continuously for a period of 9 months. Of the entire group of 67 patients, 47 (70%) had axial and proximal lesions (pelvis, spine, rib, humerus, and femur) and 20 (30%) had distal lesions (forearm, leg, and foot); 53/67 (79%) are surviving free of disease 12--118 months (median 41 months) from the start of treatment. Fifteen of 23 (65%) patients with axial lesions, 19/24 (79%) patients with proximal lesions, and 19/20 (95%) patients with distal lesions are free of disease. Disease-free survivors include 28/39 (72%) male patients and 25/28 (89%) female patients. Thirty-four patients had RT, and 33 had surgery or surgery and RT, in addition to chemotherapy, for local treatment. The disease-free survival rate was 76% in the RT group and 82% in the surgery group; failure in the RT group was attributable to local recurrence in 7/34 (21%) patients. Recent experience with T-9 CT has demonstrated that CT given prior to RT or surgery can cause a great reduction in the size of the primary tumor while allowing the pathologically-eroded bone to heal prior to the initiation of RT; this also allows the high-risk patient with an axial primary (pelvis or spine) to tolerate the aggressive CT needed to prevent distant metastases. In addition to dramatically increasing survival in patients with Ewing's sarcoma, combination CT has helped achieve permanent local control. The superior survival rates for all sites of primary tumor are attributable to the early use of aggressive combination CT.

Combination chemotherapy (T-6) in the multidisciplinary treatment of Ewing's sarcoma.

Twenty-eight patients with primary Ewing's sarcoma (ES) and 10 with primary and metastatic ES were treated with intensive induction (T-6) and maintenance sequential chemotherapy (T-2). Local treatment for the primary tumor was surgery and/or radiation therapy (RT), and the choice depended on the patient's age and the location and size of the tumor. Patients with pulmonary metastases received bilateral pulmonary RT with 1,400 rad before T-2 maintenance chemotherapy. Most patients who were given T-65 induction chemotherapy before local therapy had healing of pathologically destroyed, tumor-bearing bones before the initiation of RT. None who had RT after T-6 chemotherapy developed pathologic fractures. Of the 28 with primary ES, 23 (82%) remained free of disease for more than 12 to over 46 months (median 22+ mo). Six of 10 with primary and metastatic disease are free of disease from more than 14 to over 34 months (median, 22+ mo). In addition to producing higher survival rates in the patients with poor prognoses, T-6 chemotherapy also improved the treatment of the primary tumor and achieved better function and, it is hoped, a lower local recurrence rate following RT. We found that the timing of T-6 chemotherapy and RT was crucial to obtaining a maximal response of the primary tumor and to maintaining patient tolerance for this aggressive treatment. The long rest required after patients were given 1,3-bis (2-chloroethyl)-1-nitrosourea makes its use in future protocols undesirable.

Osteogenic sarcoma: eight-percent, three-year, disease-free survival with combination chemotherapy (T-7).

Sixty-one patients were treated with combination chemotherapy (T-7) for biopsy-proved, fully malignant, osteogenic sarcoma (OS) of the extremity. Chemotherapy consisted of the combination of bleomycin, cyclophosphamide, and dactinomycin, followed in 2 weeks by vincristine and high-dose methotrexate (HDMTX) given in doses of 8 g/m2 for adolescents and 12 g/m2 for children 12 years old or younger with citrovorum factor rescue. The HDMTX was administered weekly for 4 weeks. One week following the 4 HDMTX treatments, adriamycin (ADR) was given at a dose of 90 mg/m2 for 2 days. Two weeks after the ADR, 2 additional doses of HDMTX were given before surgery. Thirty-eight of the 61 patients were referred before amputation and underwent preoperative chemotherapy for approximately 3 months. After surgery, chemotherapy was resumed. Of the 61 consecutive patients with primary OS entered in the T-7 protocol, 54 (88%) remained free of disease for more than 8 to over 35 months (median 18+ mo), with a projected 3-year disease-free survival in excess of 80%. Of the 38 receiving T-7 chemotherapy before surgery, 28 demonstrated a near complete or complete lack of viable tumor cells on examination of the resected primary tumors. All 28 are surviving free of disease. Nine of the 10 patients less than 12 years of age remain free of disease from over 12 to more than 35 months (median 24+ mo). A significant increase in disease-free survival in the younger patients could presumably be attributed to the use of 12 g HDMTX/m2 in that age group. The prognostic value of the effect of preoperative chemotherapy on the primary tumor is statistically highly significant. These data indicated that preoperative chemotherapy with the proper dose of HDMTX would be valuable in all patients with OS.

Primary osteogenic sarcoma: the rationale for preoperative chemotherapy and delayed surgery.

From 1973--1975, 31 patients with biopsied primary osteogenic sarcoma were treated with preoperative chemotherapy followed by surgical ablation of the primary tumor. Surgery was delayed in order to obtain a custom-fitted prosthetic bone implant in an attempt to avoid amputation. Preoperative chemotherapy included high dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) and adriamycin (T-5 protocol) and was administered for 3 months preoperatively and continued with the inclusion of cyclophosphamide for approximately 5 months postoperatively. At a follow-up period of 30--52 months, 23 of 31 patients (75%) are surviving (21 of 23 with no evidence of disease). Histologic examination of primary tumor removed at surgery revealed varying degrees of tumor destruction (from very little effect to no evidence of viable tumor) attributable to the effect of chemotherapy. The 21 patients that are disease-free survivors had a more complete effect of preoperative chemotherapy on the primary tumor. Some patients achieving favorable effects upon the primary tumor did so only after the dose of HDMTX was escalated to greater than the starting dose of 8 g/m2. Preoperative chemotherapy for all patients with osteogenic sarcoma would seem to offer the following advantages: 1) Evaluation of the effect of HDMTX with CFR on the primary tumor with escalation of the dose of HDMTX until a clinical response is observed, thus defining the dose of HDMTX effective in that patient, to be continued postoperatively as adjuvant therapy; 2) The early use of systemic therapy to eradicate distant microfoci of disease that will eventually kill the patient if not adequately treated by effective chemotherapy; 3) Allow more time for postoperative healing without the need to start adjuvant chemotherapy immediately; and 4) Provide the surgeon time to plan resection surgery. To date, 20 additional patients with biopsy proven osteogenic sarcoma have been treated with more aggressive preoperative chemotherapy (T-7) for approximately 2 1/2 months prior to definitive surgery (resection or amputation). Doses of HDMTX were escalated where necessary and good clinical responses were obtained in 19 of 20 patients. In the majority of patients, no evidence of viable tumor was found on histologic examination of the surgically removed primary tumor. All 20 patients are surviving free of active disease at this brief follow-up period of 4--20 months.

Curability of Ewing's sarcoma and considerations for future therapeutic trials.

Twenty previously untreated children with primary Ewing's sarcoma and 8 children with primary tumor and metastatic disease were treated with surgery or radiation therapy (6,000-7,000 rads) for their primary tumor and T-2 chemotherapy. Of the 20 children with primary Ewing's sarcoma treated with T-2 "adjuvant" chemotherapy, 15 had no evidence of recurrent disease for from 31+-82+ months (median 46+ months) from the start of treatment. The actuarial 5-year disease-free survival rate for this group of patients was 75%. Eight patients presenting with metastatic disease had complete responses to T-2 chemotherapy, but 7/8 with metastatic disease eventually had tumor recurrence. Examination of the treatment failures, both those patients relapsing after adjuvant chemotherapy for primary Ewing's sarcoma (5), and those relapsing after having a complete response of metastatic disease (7) to T-2 chemotherapy, revealed that all relapses occurred at the end of the second year of T-2 chemotherapy or after chemotherapy was stopped. In addition, of 23 patients receiving "curative" radiation therapy to their primary tumor, 5 had local recurrence (22%) and 6 (26%) had severe functional debility secondary to combined radiation therapy and T-2 chemotherapy. The conclusions drawn from this experience have led us to consider a new approach to the treatment of Ewing's sarcoma, namely: 1) more aggressive initial or "induction" chemotherapy with subsequent T-2 "maintenance" chemotherapy to eradicate more completely all metastatic microfoci of disease presumed to be present in patients with primary tumor at the time of diagnosis, and ostensively present in patients with metastatic disease; 2) the use of surgery alone or in combination with moderate doses of radiation therapy in those patients in whom we can predict a high frequency of local recurrence (pelvic lesions) or a high percentage of "functional failures" (young children with lower extremity lesions). Preliminary results with this latter approach are encouraging with 11/13 patients with primary Ewing's sarcoma free of disease at 12+-26+ months. A longer follow-up of this more aggressive treatment is needed to determine the superiority of this approach for both increased survival and improved late physical rehabilitation.