Prevalence, risk factors, treatment uptake and treatment outcome of hepatitis C virus in people who inject drugs at the needle and syringe program in Uppsala, Sweden.

BACKGROUND: The World Health Organization has set a goal to reach world elimination of hepatitis C virus (HCV) by 2030. Needle and syringe programs (NSP) for people who inject drugs (PWID) are crucial to achieve this goal. The NSP in Uppsala, Sweden, was opened in 2016 and has since 2018 provided HCV treatment for PWID. The aim of this study was to investigate HCV prevalence, risk factors and treatment uptake and outcome in NSP participants. METHODS: Data from 450 PWID registered at the Uppsala NSP between 2016-11-01 and 2021-12-31 were collected from the national quality registry InfCare NSP. Data from the 101 PWID treated for HCV at the Uppsala NSP were collected through patient journal review. Descriptive and inferential analysis was performed. Ethical approval was obtained from the Ethical Review Board in Uppsala (dnr 2019/00215). RESULTS: The mean age was 35 years. 75% were males (336/450), and 25% were females (114/450). The overall HCV prevalence was 48% (215/450) with a declining trend over time. Factors associated with a higher risk of HCV were older age at registration (OR 1.025, 95% CI 1.004-1.046), lower age at injection drug debut (OR 0.963, 95% CI 0.932-0.996), lower education level (OR 1.829, 95% CI 1.185-2.821) and higher number of total visits at the NSP (OR 1.005, 95% CI 1.001-1.009). The overall HCV treatment uptake was 47% (101/215), of which 77% (78/101) completed HCV treatment. The HCV treatment compliance was 88% (78/89). 99% (77/78) were cured with a sustained virologic response 12 weeks after completed treatment. The reinfection rate over the study period was 9/77 (11.7%); all were male with mean age of 36. CONCLUSIONS: HCV prevalence, treatment uptake and treatment outcome have improved since the opening of the Uppsala NSP. However, further measures are needed to reach the HCV elimination goal. Outreach HCV treatment programs for PWID should be explored and evaluated in combination with further implementation of low-threshold programs.

Total overall management and surgical outcome after aneurysmal subarachnoid haemorrhage in a defined population.

It was possible from a geographically well-defined region to detect all patients sustaining an aneurysmal subarachnoid haemorrhage. Different outcomes were measured and compared with other published series. Twenty-one per cent of all our patients at risk were never seen by a neurosurgeon. By adding further 20% of dead patients to the management series a total overall outcome, i.e. from all 'patients at risk', could be calculated, making comparison between different series easier. Favourable outcomes in the three groups (total overall, total management and surgical) as measured with the Glasgow Outcome Scale at 12 months were 46, 58 and 69%, respectively, in this series. In a super selected group such as good-grade patients (Hunt and Hess I-II) at surgery favourable results were seen in 87% of the patients at 6 months follow-up. The favourable outcome in the total overall, total management and surgical groups increased between 6 and 12 months follow-up by 1, 1 and 2%, respectively, as compared to 4, 5 and 6%, respectively, between discharge and 6 months follow-up. The time of follow-up to measure outcome should not be shorter than 6 months in aneurysm cases. It is emphasized that all patients drop-outs from the initial 'patient at risk' should be identified.

Effect of the calcium antagonist nimodipine on the delayed hypoperfusion following incomplete ischemia in the rat.

Regional cerebral blood flow (CBF) was measured autoradiographically in the recovery period following 15 min of forebrain ischemia in rats pretreated with either nimodipine (0.1 mg kg-1) or vehicle. The results showed that although nimodipine increased postischemic CBF, the flow enhancement was regionally heterogeneous, sometimes resulting in zones of gross hypoperfusion and overt hyperemia within the same structures. This patchy improvement of delayed postischemic hypoperfusion was not accompanied by recovery of sensory evoked responses, and return of EEG activity was not enhanced.

Tissue lactic acidosis and ischemic brain damage.

Current evidence suggests that the brain has considerable potential to tolerate prolonged periods of complete ischemic anoxia. Moreover, the brain may be less damaged by complete ischemic anoxia than by severe incomplete ischemia. The accumulation of lactic acid in the brain during severe incomplete ischemia approaches three times the levels seen with complete ischemic anoxia, and this phenomenon is implicated in exacerbated biochemical and structural injury.

Cyclo-oxygenase inhibition by indomethacin and recirculation following cerebral ischemia.

In this study we examined the effect of pretreatment with the cyclo-oxygenase inhibitor indomethacin (10 mg . kg-1) on local cerebral blood flow (DBF) in the immediate recirculation period following complete and incomplete ischemia. Ischemia of 15 min duration was induced in lightly anaesthetized and artificially ventilated rats, and local CBF was measured with a 14C-iodoantipyrine autoradiographic technique after recirculation periods of 5 min. Following complete ischemia indomethacin-treated animals showed a reduced incidence of perfusion defects of the "no-reflow" type. Perfused structures had somewhat higher flow rates than in untreated rats. A similar enhancement of immediate reflow was observed following incomplete ischemia provided that the structures in question had been severely ischemic. In structures that suffered only mild ischemia, the drug reduced postischemic CBF. It is concluded that, in the rat brain, cyclo-oxygenase inhibition does not curtail postischemic reactive hyperemia. Furthermore, the previously reported beneficial effect of indomethacin on brain circulation following complete ischemia seems to be due to an enhancement of immediate reflow, and to amelioration of an initial hindrance to reflow.

Cerebral circulatory responses to hypercapnia and hypoxia in the recovery period following complete and incomplete cerebral ischemia in the rat.

In this study we examined the reactions of cerebral vessels to hypercapnia and hypoxia during the recovery period following cerebral ischemia. We used ventilated, lightly anesthetized rats and induced complete ischemia by CSF compression, incomplete ischemia by bilateral carotid occlusion combined with hypotension. After 15 min of ischemia and 60 min of recirculation the animals were rendered hypercapnic or hypoxic for 2-3 min and local CBF was then measured autoradiographically with 14C-iodoantipyrine. Following complete ischemia vascular CO2 responsiveness was abolished or attenuated in most structures analysed. However, there was a considerable interstructural heterogeneity. For example, in the cerebellum and the red nucleus flow rates were observed which approached values obtained in hypercapnic control animals, whereas CO2 responsiveness was abolished in several cortical areas and hippocampus. The response to CO2 following incomplete ("forebrain") ischemia varied considerably. In the cerebral cortices areas with low flow rates were often mixed with hyperemic zones, and in most structures that had very low flow rates during ischemia, CO2 responsiveness was lost or grossly attenuated. Structures that had suffered moderate or only mild ischemia had better retained or completely preserved CO2 response. The cerebrovascular reaction to hypoxia was found to be attenuated in most, but not abolished in any of the structures examined. In general, the vascular response to hypoxia was better preserved than that to hypercapnia. Reactivity was similar following complete and incomplete ischemia. As observed during hypercapnia, there were pronounced interstructural variations with considerable increases in flow rates e.g. in the substantia nigra and the cerebellum.

Local cerebral blood flow in the recovery period following complete cerebral ischemia in the rat.

This study examines reflow patterns in the recirculation period following complete, global ischemia. Cerebrospinal fluid (CSF) compression ischemia was induced in ventilated rats for 5-30 min, and local cerebral blood flow (CBF) was measured autoradiographically after 5, 60, and 90 min of recirculation. Ischemia of 15 min duration was induced by four-vessel occlusion combined with arterial hypotension in two additional groups, with recovery periods of 5 or 60 min. In the immediate recirculation period (5 min), following 15 min of ischemia, local CBF was markedly heterogeneous. Thus, whereas most structures gave clear evidence of "reactive hyperemia," others showed perfusion defects of the "no-reflow" type. Typically these defects affected the striatum, thalamus, and hippocampus, as well as the frontal, sensorimotor, and parietal cortices. Areas of no-reflow appeared after 10 min, were more extensive after 15 min, and occupied a major part of the brain after 30 min of ischemia. When recirculation was instituted for 60 or 90 min, following 15 min of ischemia, flow returned in previously unperfused areas. However, a delayed hypoperfusion developed, which differed widely between structures (range of CBF values, 20-80% of control). When the ischemic period was prolonged to 30 min, some perfusion defects remained, even after 90 min of recirculation.

Recirculation in the rat brain following incomplete ischemia.

The objective of this study was to characterize local cerebral blood flow (CBF) in the recirculation period following incomplete forebrain ischemia. Specifically, we wished to determine whether perfusion defects developed in the immediate recirculation period, to study how initial hyperemia and delayed hypoperfusion at the local level were related to the severity of the preceding ischemia, and to find out whether reflow was influenced by the nutritional state of the animals. To that end, forebrain ischemia of 15 min duration was induced in fed and fasted ventilated rats under 70% N2O. Local CBF was measured with an autoradiographic technique at the end of ischemia, as well as at 5 and 60 min following the start of recirculation. Control experiments were performed to examine the influence of ischemia on cerebral metabolic state in fed and fasted animals. The ischemia reduced CBF to excessively low values (less than 5% of control) in many forebrain structures, including the cerebral cortices, caudoputamen, and hippocampus. In spite of this, perfusion defects failed to appear after 5 min of recirculation. Instead, moderate to marked hyperemia was present in all previously ischemic structures. After 60 min of recirculation, pronounced hypoperfusion developed. The magnitude of the initial hyperemia was poorly related to the severity of the preceding ischemia, but the latter partly determined the degree of delayed hypoperfusion. Thus, little or no hypoperfusion developed in structures whose flow rates exceeded 30-40% of control during ischemia. Fasted animals had a better preserved flow to many structures than did fed animals, indicating that the detrimental effect of feeding (or glucose infusion) is also reflected in lower perfusion rates.

Temporary clipping during early operation for ruptured aneurysm: preliminary report.

Temporary arterial occlusion was performed in 16 patients undergoing early aneurysm operation. Ten patients had a ruptured middle cerebral artery (MCA) aneurysm, and 6 had a ruptured anterior communicating artery aneurysm. Premature aneurysm rupture during operation necessitated temporary arterial occlusion in 10 patients. In 5 patients, temporary arterial occlusion was performed to facilitate dissection of the aneurysm. In 1 patient with a large MCA aneurysm, temporary occlusion was performed to provoke collapse of the completely exposed aneurysm sac, thus making clipping of the base possible. The results do not indicate that temporary occlusion by the standard aneurysm clips now in general use leads to angiographically detectable arterial wall changes or increased thromboembolic complications. Temporary clipping of the MCA proximal to the perforating arteries may be well tolerated for up to 20 minutes during early aneurysm operation. Temporary occlusion of one or both anterior cerebral arteries or temporary pericallosal clipping need not unconditionally lead to disastrous consequences if rendered necessary during aneurysm operations performed in the acute stage.

Influence of blood glucose concentration on brain lactate accumulation during severe hypoxia and subsequent recovery of brain energy metabolism.

The effects of hypoxaemia on regional cerebral blood flow (CBF) and brain cortical metabolite concentrations were investigated at different blood glucose concentrations in rats under nitrous oxide anaesthesia. Tissue hypoxia of 15-min duration was induced by a combination of arterial hypoxaemia, hypotension, and clamping of the right carotid artery. Blood glucose concentrations were manipulated by varying the food intake in the 24 h before the experiment, and by glucose administration. Cortical CBF doubled during hypoxia on the intact side, but did not differ significantly from control values on the clamped side. In the clamped hemisphere there was a substantial decrease in adenylate energy charge. At brain tissue glucose concentration of 1 mumol g-1 and above, there was an inverse correlation between adenylate energy charge and brain lactate concentration. In starved animals with mean brain glucose of 0.32 +/- 0.00 mumol g-1, lactate concentration was significantly lower, in spite of equally severe disruption of energy state. Recovery of brain adenylate energy charge was worse in fed and glucose-infused groups than in the fasted group. These results demonstrate that limitation of substrate supply during severe hypoxia in the rat allows enhanced recovery of brain energy metabolism following the hypoxic episode.

Results of early operations for ruptured aneurysms.

In a consecutive series of 219 patients with a ruptured aneurysm of the anterior part of the circle of Willis, 119 patients (54%) made a good recovery and 67 (31%) died. Of 53 patients who did not have surgery, six (11%) made a good recovery and 37 (70%) died. Urgent surgery with evacuation of an associated significant intracerebral hematoma was performed in 30 patients; nine (30%) made a good recovery and 15 (50%) died. Delayed surgery was performed in 55 patients of whom 42 (76%) made a good recovery and two (4%) died. Early intracranial operation (within 48 to 60 hours after subarachnoid hemorrhage (SAH)) was performed in 81 patients who were in Grades I to III prior to surgery. Sixty patients (74%) made a good recovery, and eight died within a month. Five patients were severely disabled and died 2 to 8 months after SAH and surgery. In 17 patients, although the immediate postoperative course was uneventful, evidence of cerebral ischemia developed 4 to 13 days after the bleed and resulted in death in eight patients. A poor outcome was correlated with a history of elevated blood pressure before SAH. Seven patients, of whom six were women of child-bearing age, demonstrated pronounced vasospasm on postoperative angiography; nevertheless, they remained well and free from ischemic symptoms after surgery. Early operation combined with removal of subarachnoid clots and rinsing the basal cisterns does not eliminate the risk of delayed ischemic dysfunction. Such early surgery, however, improves overall outcome by preventing recurrent bleeding, and may also reduce the frequency of hydrocephalus.

Motion of bones and volume changes in the neurocranium after craniectomy in Crouzon's disease. A roentgen stereometric study.

Craniectomy was performed on a boy with Crouzon's disease at 22 months of age. Metallic implants (tantalum balls, 0.5 mm in diameter) were inserted in the calvaria during surgery, and the child was examined postoperatively by roentgen stereometry at intervals of about 100 days (total observation time, 309 days). The thyroid radiation dose was 250 muGy for one examination. The effect of craniectomy was recorded with a high degree of accuracy in terms of motion of bones and volume changes in the calvaria. Expansion occurred almost entirely through motion of free bone flaps in the frontal region, while a linear craniectomy in the region of the sagittal suture caused small changes. The rate of expansion decreased rapidly and stabilization was recorded about 250 days after surgery.

Aspects on the treatment of gliomas of the anterior visual pathway.

Partial excision of the glioma of the anterior visual pathway seemed to have no effect on the vision in 7 patients and had a negative effect in 2. These results support the opinion that no excision should be made in such tumours. However, the course of the disease in one exceptional patient raises doubts about the general validity of this rule. In this case the postulated chiasmal glioma proved to be an exophytic glioma arising in one intracranial optic nerve and compressing the other. Excision of the exophytic portion caused rapid and considerable improvement of vision in both eyes. Direct visualization by craniotomy was needed to separate this mode of growth from the common intrinsic growth of such tumours.