Empirical evidence for definitions of episode, remission, recovery, relapse and recurrence in depression: a systematic review.

AIMS.: For the past quarter of a century, Frank et al.'s (1991) consensus-based definitions of major depressive disorder (MDD) episode, remission, recovery, relapse and recurrence have been the paramount driving forces for consistency in MDD research as well as in clinical practice. This study aims to review the evidence for the empirical validation of Frank et al.'s proposed concept definitions and to discuss evidence-based modifications. METHODS.: A literature search of Web of Science and PubMed from 1/1/1991 to 08/30/2017 identified all publications which referenced Frank et al.'s request for definition validation. Publications with data relevant for validation were included and checked for referencing other studies providing such data. RESULTS.: A total of 56 studies involving 39 315 subjects were included, mainly presenting data to validate the severity and duration thresholds for defining remission and recovery. Most studies indicated that the severity threshold for defining remission should decrease. Additionally, specific duration thresholds to separate remission from recovery did not add any predictive value to the notion that increased remission duration alleviates the risk of reoccurrence of depressive symptoms. Only limited data were available to validate the severity and duration criteria for defining a depressive episode. CONCLUSIONS.: Remission can best be defined as a less symptomatic state than previously assumed (Hamilton Rating Scale for Depression, 17-item version (HAMD-17) ⩽4 instead of ⩽7), without applying a duration criterion. Duration thresholds to separate remission from recovery are not meaningful. The minimal duration of depressive symptoms to define a depressive episode should be longer than 2 weeks, although further studies are required to recommend an exact duration threshold. These results are relevant for researchers and clinicians aiming to use evidence-based depression outcomes.

Will you still need me, will you still feed me when I'm 64? The health impact of caregiving to one's spouse.

Informal care may substitute for formal long-term care that is often publicly funded or subsidized. The costs of informal caregiving are borne by the caregiver and may consist of worse health outcomes and, if the caregiver has not retired, worse labor market outcomes. We estimate the impact of providing informal care to one's partner on the caregiver's health using data from the Survey of Health, Ageing, and Retirement in Europe. We use statistical matching to deal with selection bias and endogeneity. We find that in the short run caregiving has a substantial effect on the health of caregivers and, for female caregivers, on their health care use. These effects should be taken into account when comparing the costs and benefits of formal and informal care provision. The health effects may, however, be short-lived, as we do not find any evidence that they persist after 4 or 7 years.

The supercoiling state of DNA determines the handedness of both H3 and CENP-A nucleosomes.

Nucleosomes form the unit structure of the genome in eukaryotes, thereby constituting a fundamental tenet of chromatin biology. In canonical nucleosomes, DNA wraps around the histone octamer in a left-handed toroidal ramp. Here, in single-molecule magnetic tweezers studies of chaperone-assisted nucleosome assembly, we show that the handedness of the DNA wrapping around the nucleosome core is intrinsically ambidextrous, and depends on the pre-assembly supercoiling state of the DNA, i.e., it is not uniquely determined by the octameric histone core. Nucleosomes assembled onto negatively supercoiled DNA are found to exhibit a left-handed conformation, whereas assembly onto positively supercoiled DNA results in right-handed nucleosomes. This intrinsic flexibility to adopt both chiralities is observed both for canonical H3 nucleosomes, and for centromere-specific variant CENP-A nucleosomes. These data support recent advances suggesting an intrinsic adaptability of the nucleosome, and provide insights into how nucleosomes might rapidly re-assemble after cellular processes that generate positive supercoiling in vivo.

[Periprosthetic Acetabulum Fractures]. / Periprothetische Azetabulumfrakturen.

In contrast to periprosthetic fractures of the femur, periprosthetic fractures of the acetabulum are rare complications - both primary fractures and fractures in revision surgery. This topic is largely under-reported in the literature; there are a few case reports and no long term results. Due to an increase in life expectancy, the level of patients' activity and the number of primary joint replacements, one has to expect a rise in periprosthetic complications in general and periprosthetic acetabular fractures in particular. This kind of fracture can be intra-, peri- or postoperative. Intraoperative fractures are especially associated with insertion of cementless press-fit acetabular components or revision surgery. Postoperative periprosthetic fractures of the acetabulum are usually related to osteolysis, for example, due to polyethylene wear. There are also traumatic fractures and fractures missed intraoperatively that lead to some kind of insufficiency fracture. Periprosthetic fractures of the acetabulum are treated conservatively if the implant is stable and the fracture is not dislocated. If surgery is needed, there are many possible different surgical techniques and challenging approaches. That is why periprosthetic fractures of the acetabulum should be treated by experts in pelvic surgery as well as revision arthroplasty and the features specific to the patient, fracture and prosthetic must always be considered.

Loss of spatial organization and destruction of the pericellular matrix in early osteoarthritis in vivo and in a novel in vitro methodology.

OBJECTIVES: Current repair procedures for articular cartilage (AC) cannot restore the tissue's original form and function because neither changes in its architectural blueprint throughout life nor the respective biological understanding is fully available. We asked whether two unique elements of human cartilage architecture, the chondrocyte-surrounding pericellular matrix (PCM) and the superficial chondrocyte spatial organization (SCSO) beneath the articular surface (AS) are congenital, stable or dynamic throughout life. We hypothesized that inducing chondrocyte proliferation in vitro impairs organization and PCM and induces an advanced osteoarthritis (OA)-like structural phenotype of human cartilage. METHODS: We recorded propidium-iodine-stained fetal and adult cartilage explants, arranged stages of organization into a sequence, and created a lifetime-summarizing SCSO model. To replicate the OA-associated dynamics revealed by our model, and to test our hypothesis, we transduced specifically early OA-explants with hFGF-2 for inducing proliferation. The PCM was examined using immuno- and auto-fluorescence, multiphoton second-harmonic-generation (SHG), and scanning electron microscopy (SEM). RESULTS: Spatial organization evolved from fetal homogeneity, peaked with adult string-like arrangements, but was completely lost in OA. Loss of organization included PCM perforation (local micro-fibrillar collagen intensity decrease) and destruction [regional collagen type VI (CollVI) signal weakness or absence]. Importantly, both loss of organization and PCM destruction were successfully recapitulated in FGF-2-transduced explants. CONCLUSION: Induced proliferation of spatially characterized early OA-chondrocytes within standardized explants recapitulated the full range of loss of SCSO and PCM destruction, introducing a novel in vitro methodology. This methodology induces a structural phenotype of human cartilage that is similar to advanced OA and potentially of significance and utility.

A non-comparative phase II study of dose intensive chemotherapy with doxorubicin and ifosfamide followed by high dose ICE consolidation with PBSCT in non-resectable, high grade, adult type soft tissue sarcomas.

The objective was to determine the role of dose intensive induction chemotherapy in patients with soft tissue sarcomas (STS) that were considered unresectable. Treatment consisted of 2-3 cycles of doxorubicin (Dox) and ifosfamide (Ifo) followed by high dose chemotherapy with ifosfamide, carboplatin, etoposide (HD-ICE) plus peripheral blood stem cell transplantation (PBSCT). 30 out of 631 consecutive patients, median age 46 years (21-62), with high grade STS were included. 29 patients completed at least 2 cycles of Dox/Ifo. HD-ICE was withheld because of progressive disease (PD) in 5 patients, neurotoxicity in 6 cases, insufficient peripheral blood stem cell (PBSC) mobilization, complete remission (CR) and refusal in 1 patient each. HD-ICE was associated with non-haematological grade III toxicity including emesis, mucositis, fever, neurotoxicity, and transaminase level elevation. Two additional patients attained a partial response after HD-ICE. Overall, 24 of 30 (80%) patients underwent surgery, with complete tumor resections in 19 patients (63% of all patients, 79% of the operated subgroup); however, 2 of these required amputation. After a median follow up period of 50 months in surviving patients (range, 26-120), 5-year PFS and OS rates were 39% and 48%, respectively. Induction chemotherapy plus consolidation HD-ICE is generally feasible, but is associated with significant neurotoxicity. The advantage of HD-ICE over conventional dose chemotherapy plus external beam radiation therapy (EBRT) in non-resectable disease remains unproven.

[Value of microvascular, free flap transplantation in treatment of open tibial fracture]. / Der Stellenwert der mikrovaskulären, freien Lappentransplantation in der Behandlung der offenen Unterschenkelfraktur.

Between 1986 and 1994, 71 cases of open fractures of the lower leg were treated by transplantation of a free, microvascular flap. Of these, 68 flaps were successful and the complication rate was low. Because of better vascularity subsequent bone reconstruction was shown to be more effective.

[C-reactive protein as infection parameter in clinically suspected postoperative infection after trauma surgery and orthopedic interventions. 2]. / CRP als Infektionsparameter bei klinischem Verdacht auf eine postoperative Infektion nach unfallchirurgischen und orthopädischen Eingriffen. Teil 2 im Anschluss an Beitrag siehe Heft 5/94.

Prospectively the levels of C-reactive protein (CRP) of 40 patients were studied twice within 6-12 hours in case of a suspected infection after different osteosynthetic and orthopedic procedures and compared with the levels of the erythrocyte sedimentation rate (ESR). 16 patients showed an increase of CRP in relation to a wound infection, hematoma or effusion in all but one case. 6 patients showed an increase of ESR, which also could be cleared in all but one case. Those patients with a proved wound infection demonstrated a CRP-rise in 8 cases, a CRP-plateau in 4 cases and no CRP-decrease. The same patients showed an ESR-rise in 3, an ESR-plateau in 7 and an ESR-decrease in even 2 cases. This study indicates that the determination of two CRP-levels with a short interval in case of a clinically suspected infection is another, meaningful criterion in making a decision for an operative revision.

[C-reactive protein as a postoperative parameter of infection in hip joint replacement and knee joint operations]. / CRP als postoperativer Infektionsparameter bei Hüftgelenksersatz- und Kniegelenksoperationen (Teil 1).

Prospectively 70 male patients with elective arthroplasty of the hip (n = 34) and with operation of the anterior cruciate ligament (n = 36) were studied in respect of the postoperative screening of C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), the white blood cell count and the clinical signs of infection. There were 9 infectious postoperative complications, all with an increase of CRP. But also 6 other patients with no clear infection showed a rise or a plateau of CRP, which could only be explained by the presence of a hematoma, an effusion or a subclinical infection. The close postoperative screening of CRP appeared to be quite costly and laborious, especially in a population with a low infection rate. We therefore suggest a CRP-screening only on patients or operative procedures with wellknown high risk. In addition we studied the determination of two CRP-levels with a short interval following the clinical suspect of a postoperative infection (described in part II of this paper).

[Subacute and chronic epidural hematoma after craniocerebral trauma]. / Subakute und chronische epidurale Hämatome nach Schädel-Hirn-Trauma.

During an 8-year period, fifteen patients with subacute or chronic epidural haematoma were seen among 110 treated cases of extradural haematoma corresponding to a frequency of 13.6%. Increasing headache, nausea, vomiting, mild drowsiness and cranial nerve palsy were the symptoms resulting in the correct diagnosis in most cases. Clinical and pathological findings are described, and the factors influencing the course of events are discussed. The most important factors are cerebral atrophy, age, source of bleeding and location. By means of early CT (computed tomography) diagnosis of haematoma, fatal outcome could be prevented in most of the cases.

Isradipine twice daily lowers blood pressure over 24 H.

The objective of this study was to compare the effects of isradipine and placebo on blood pressure (BP) at the end of the dosing interval ('trough'). Following a three-week placebo period, 187 patients who had previously shown a response to treatment with isradipine (based on office BP measurements) were randomized to double-blind treatment with 2.5 mg isradipine twice daily or placebo for six weeks. Four of these patients withdrew from the study during the double-blind phase because of adverse events (one taking isradipine and three taking placebo). Blood pressure during the double-blind study was always measured 12 h after drug administration (trough values). The rate of normalization [defined as diastolic BP (DBP) less than or equal to 90 mm Hg] was 52/96 (54%) in the isradipine-treated group compared with 30/87 (33%) in the placebo group. A further 12/96 (12%) patients taking isradipine showed a fall in DBP of greater than or equal to 10 mm Hg, although their DBP was still not less than 90 mm Hg, compared with 5/87 (6%) patients receiving placebo. This difference was statistically significant (P = .003). Thus, isradipine in a dose of 2.5 mg twice daily lowers blood pressure over 24 h.

Nizatidine versus ranitidine in the treatment of peptic ulcer disease: report on the Dutch investigation as part of a European multicentre trial.

The efficacy and safety of nizatidine was evaluated in comparison with ranitidine in 230 patients with endoscopically documented gastric (71) or duodenal (159) ulcers. Gastric ulcer patients who satisfied all criteria for inclusion and exclusion were randomly allocated to nizatidine 300 mg nocte, 150 mg b.d. or ranitidine 150 mg b.d., duodenal ulcer patients to nizatidine 300 mg nocte or ranitidine 300 mg nocte. Endoscopic healing was defined as complete epithelialisation of all mucosal lesions. Endoscopy was performed at 4 and, if not healed, at 8 weeks. Healing rates were shown to be comparable for all treatment regimens. In both duodenal ulcer treatment groups, and with both drugs, healing was negatively influenced by ulcer size, ulcer number, smoking habits and a disease duration of 5 years or more. Few side effects were noted. Nizatidine, administered as a 300 mg nocte and as a 150 mg b.d. dose appeared to be a safe H2 antagonist and was as effective as ranitidine in the treatment of duodenal and gastric ulceration.